Born in London, England in 1951 to Leonard George and Elsie Cressy Houghton, he was raised in a working-class family along with elder brother Graham. Educated at an excellent government primary school (Lyndhurst Grove) until the age of 11, he then won a scholarship to Alleyn’s School in Dulwich, London, founded by Edward Alleyn, a lead actor and producer of William Shakespeare’s plays in the 16th and 17th centuries. Graduating with college entry examinations in physics, chemistry and math, he decided to study biology at college, having been heavily influenced by reading at age 17 about the life and works of Louis Pasteur and also watching BBC TV coverage of the discovery of the DNA double helix early on Sunday mornings. In 1969, he entered the school of Biological Sciences at the new University of East Anglia, where he was highly motivated by the teachings of Professors Balls, Wilden and Thane as well as by full extracurricular activities including playing for the college cricket and squash teams. Offered attractive PhD positions at a London cancer research center, Oxford University, and Glasgow University, he failed to secure a stipend so entered the research laboratories of GD Searle & Co. in High Wycombe, UK, which was engaged in basic molecular biology research. Registering for a PhD in Biochemistry at King’s College, University of London in 1973 and co-supervised by Dr. Norman Carey (Searle) and Dr. James Chesterton (King’s), he graduated with a PhD in 1977 in a ceremony at the Alberta Hall with his wife, Han Fong Ida, who received her B. Pharm degree at the same ceremony from the London School of Pharmacy.

He then continued as a Research Investigator at Searle, benefiting from the excellent mentorship of Dr. Norman Carey and Dr. Richard Palmiter, where he characterized the human fibroblast interferon gene using newly emerging recombinant DNA technology. Offered many positions at burgeoning genetic engineering companies in the UK and US, in 1982 he chose to join the Chiron Corporation in California, founded by University of California Professors Bill Rutter and Ed Penhoet. Intending originally to work on chimeric type 1 interferons and to identify what became known later as type 3 interferons, he was introduced to the problem of Non-A, Non-B hepatitis by Dr. Dino Dina, then Director of Virology at Chiron. As a result, he decided to devote his laboratory to the pursuit of the causative agent(s) of this infectious disease, using a molecular biological approach, which was known not to be caused by the already charac- terized hepatitis A & B viruses. After pursuing numerous avenues unsuccessfully for many years, along with Dr. Qui-Lim Choo in his own laboratory, Chiron collaborator Dr. George Kuo, and CDC collaborator Dr. Dan Bradley, he published on the discovery of the hepatitis C virus (HCV) genome in 1989 with his collaborators, having published on the novel structure of the HDV genome in 1986. Following the HCV discovery, he and collaborators developed a series of patient diagnostics and blood screening tests that prevented post-transfusion hepatitis globally, as well as contributing to the identification of key enzymes crucial to the virus life cycle, which then became drug development targets for the field.

HCV infection represents a serious pandemic and so again with Dr. Choo and Dr. Kuo along with Dr. Ralston and others, he published the first evidence for an efficacious HCV vaccine in 1994 and subsequently performed 4 clinical trials in 3 different countries. His work has indicated the feasibility of developing an HCV vaccine, which he hopes to roll out to high-risk groups by the mid-2020s using both adjuvanted recombinant protein approaches as well as by applying the new RNA vaccine technologies at the Li Ka Shing Applied Virology Institute at the University of Alberta in Edmonton, Canada. He is also working with and supporting other leaders at the University of Alberta to develop a vaccine for Group A Streptococcus, and better drugs to treat Alzheimer’s disease and CMV infections. Now that HCV is a curable disease, he and others in the hepatology field are also turning their attention to the problem of non-alcoholic liver disease.

Education

1969–1972 BSc (Honors) Biological Sciences, University of East Anglia, Norwich, England

1973–1977 PhD Biochemistry, King’s College, University of London England

2019/7 Honorary Doctorate of Science University of East Anglia. Norwich, England

Positions

1977–1982 Research Investigator, Human Interferon Genetics, Searle Research Laboratories, Buckinghamshire, England

1982–1988 Project Leader, Non-A, Non-B Hepatitis Discovery Research, Chiron Corporation, Emeryville, CA

1988–2000 Director, Hepatitis C Research, Chiron Corporation, Emeryville, CA

2000–2003 Vice-President, Hepatitis C Research, Chiron Corporation, Emeryville, CA

2003–2006 Vice-President, Hepatitis C & Virology Research, Chiron Corporation, Emeryville, CA

2006–2007 Vice-President, Hepatitis C & Virology Research, Novartis Vaccines & Diagnostics, Inc., Emeryville, CA

2007–2009 Chief Scientific Officer, Epiphany Biosciences Inc., San Francisco, CA

2010–2018 Canada Excellence Research Chair in Virology and Li Ka Shing Professor, Department of Medical Microbiology and Immunology, University of Alberta Edmonton, AB, Canada

2013 – present Director of the Li Ka Shing Applied Virology Institute, University of Alberta, Edmonton, AB, Canada

Awards/Honors

The following honors were awarded for research on hepatitis C:

1992 Co-recipient of the Karl Landsteiner Award from the American Association of Blood Banks

1993 Co-recipient of the Robert Koch Medal from Germany

1993 Honoree of the Japanese Medical Congress

1993 Honoree of the Triennial International Hepatitis Meeting

1994 Co-recipient of the William Beaumont Prize from the American Gastroenterology Association

1994 Recipient of Beatrice Bitiello Award from Italian Association for Prevention of Viral Hepatitis

1994 Awardee of the Princess Takamatsu Cancer Research Fund from Japan

1998 Co-recipient of the International Hepatitis Foundation Award

1999 Co-recipient of the Hans Popper Award (Falk Foundation, Germany)

2000 Co-recipient of the Clinical Lasker Award (USA)

2005 Co-recipient of the Dale Smith Memorial Award of the American Association of Blood Banks

2009 Recipient of the Hepdart Lifetime Achievement Award (USA)

2011 Gold Medal from the Canadian Association for the Study of the Liver (CASL)

2011 The Australian Society for Microbiology Annual Scientific Meeting Bazeley Oration

2013 International Gairdner Award (Canada; declined)

2018 American Liver Foundation Distinguished Scientific Achievement Award (USA)

2020 The Nobel Prize in Medicine (The Nobel Foundation)

2021 Knighthood awarded by Queen Elizabeth II

Publications (by subject area and chronological order)

Transcriptional and Translational Control in Eukaryotes

Houghton M, Cox RF. (1974) The purification and properties of hen oviduct Form B DNA-dependent RNA polymerase. Nucl. Acids Res. 1:299–308.

Doel MT, Houghton M, Cook EA, Carey NH. (1977) The presence of ovalbumin mRNA coding sequences in multiple restriction fragments of chicken DNA. Nucl. Acids. Res. 4:3701–13.

Lilley DMJ, Houghton M. (1979) The interaction and RNA polymerase II from wheat with supercoiled and linear plasmid templates. Nucl. Acids. Res. 6:507–23.

Lilley DMJ, Jacobs MF, Houghton M. (1979) The nature of the interaction of nucleosomes with eukaryotic RNA polymerase II. Nucl. Acids Res. 7:377–99.

Lane CD, Colman A, Mohun T, Morser J, Champion J, Kourides I, Craig R, Higgins S, James TC, Applebaum SW, Ohlsson RI, Pauchas E, Houghton M, Matthews J, Miflin BJ. (1980) The Xenopus oocyte as a surrogate secretory system. Eur. J. Biochem. 111:225–35.

Sumikawa K, Houghton M, Emtage JS, Richards BM, Barnard EA. (1981) Active multi-subunit ACh receptor assembled by translation of heterologous mRNA in Xenopus oocytes. Nature. 292:862–4.

Sumikawa K, Houghton M, Smith JC, Bell L, Richards BM, Barnard EA. (1982) The molecular cloning and characterization of cDNA coding for the alpha subunit of the acetylcholine receptor. Nucl. Acids Res. 10:5809–22.

Kenten JH, Molgaard HV, Houghton M, Derbyshire RB, Viney J, Bell LO, Gould HJ. (1982) Cloning and sequence determination of the gene for the human immunoglobulin epsilon chain expressed in a myeloma cell line. Proc. Natl. Acad. Sci. USA. 79:6661–5.

Sumikawa K, Houghton M, Miledi R, Barnard EA. (1983) “A study of the mRNA and genes coding for the nicotinic acetylcholine receptor” in Cell Surface Receptors (Strange PG. ed.) pp. 249–69. Ellis Horwood Ltd., U.K.

Barnard EA, Houghton M, Miledi R, Richards BM, Sumikawa K. (1982) Molecular genetics of the acetyl choline receptor and its insertion and organization in the membrane. Biol. Cell. 45:383.

Molecular Genetics of Human Fibroblast Interferon

Houghton M, Stewart AG, Doel SM, Emtage JS, Eaton MAW, Smith JC, Patel TP, Lewis HM, Porter AG, Birch JR, Cartwright T, Carey NH. (1980) The amino– terminal sequence of human fibroblast interferon as deduced primers. Nucl. Acids Res. 8:1913–31.

Houghton M. (1980) Human interferon gene sequences. Nature. 285:536.

Houghton M, Eaton MAW, Stewart AG, Smith JC, Doel SM, Catlin GH, Lewis HM, Patel TP, Emtage JS, Carey NH, Porter AG. (1980) The complete amino acid sequence of human fibroblast interferon as deduced using synthetic oligodeoxyribonucleotide primers of reverse transcriptase. Nucl. Acids Res. 8:2885–94.

Houghton M, Jackson IJ, Porter AG, Doel SM, Catlin GH, Barber C, Carey NH. (1981) The absence of introns within a human fibroblast interferon gene. Nucl. Acids Res. 9:247–66.

Houghton M, Doel SM, Catlin GH, Stewart AG, Porter AG, Tacon WCA, Eaton MAW, Emtage JS, Carey NH. (1981) “The cloning and expression of a human fibroblast interferon gene in bacteria” in Proceedings of the Battelle International Genetic Engineering Conference (Keenberg M. ed.). Battelle Seminars and Studies Program.

McCullagh KG, Davies JA, Sim IS, Dawson KM, O’Neill GJ, Doel SM, Catlin GH, Houghton M. (1983) Biological properties of human interferon beta 1 synthesized in recombinant bacteria. J. Interf. Res. 3:97–111.

Porter AG, Bell LD, Adai JR, Catlin GH, Clarke JM, Davies JA, Dawson KM, Derbyshire RB, Doel SM, Dunthorne L, Finlay ME, Hall J, Houghton M, Hynes C, Lindley IJ, Nugent ME, O’Neill GJ, Smith JC, Stewart AG, Tacon WC, Viney JH, Warburton N, Boseley PG, McCullagh KG. (1985) “Active hybrids formed between human beta and alpha interferons” in The Biology of the Interferon System (Schellekers and Stewart eds.).

Porter AG, Bell LD, Adai JR, Catlin GH, Clarke JM, Davies JA, Dawson KM, Derbyshire RB, Doel SM, Dunthorne L, Finlay ME, Hall J, Houghton M, Hynes C, Lindley IJ, Nugent ME, O’Neill GJ, Smith JC, Stewart AG, Tacon WC, Viney JH, Warburton N, Boseley PG, McCullagh KG (1986) Novel modified beta interferons: gene cloning, expression and biological activity in bacterial extracts. DNA. 5:137–48.

Hepatitis Delta Virus

Wang KS, Choo QL, Weiner AJ, Ou JH, Najarian RC, Thayer RM, Mullenbach GT, Denniston KJ, Gerin JL, Houghton M. (1986) The structure, sequence and expression of the hepatitis delta (δ) viral genome. Nature. 323:508–14. Erratum in Nature. (1987) 328: 456.

Wang K-S, Choo Q-L, Weiner AJ, Ou J-H, Denniston KJ, Gerin JL, Houghton M (1987) “The Viroid-like structure of the hepatitis delta genome: synthesis of a viral antigen in recombinant bacteria” in The Hepatitis Delta Virus and its Infection (Rizzetto M, Gerin JL, Purcell RH. eds.) pp. 71–82. Alan Liss Inc., New York.

Weiner AJ, Wang K-S, Choo Q-L, Gerin JL, Bradley DW, Houghton M. (1987) Hepatitis delta (δ) cDNA clones: Undetectable hybridization to nucleic acids from infectious Non-A, Non-B hepatitis materials and hepatitis B DNA. J. Med. Virol. 21: 239–47.

Weiner AJ, Choo Q-L, Wang K-S, Govindarajan S, Redeker AG, Gerin JL, Houghton M. (1988) A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta. J. Virol. 62:594–9.

Weiner AJ, Choo Q-L, Wang K-S, Govindarajan S, Redeker AG, Gerin JL, Houghton M. (1988) A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta. J. Virol. 62:594–9.

Ponzetto A, Eckart M, D’Urso N, Negro F, Silvestro M, Bonino F, Wang KS, Chien D, Choo Q-L, Houghton M. (1993) Towards a vaccine for the prevention of hepatitis delta virus superinfection in HBV carriers. Prog. Clin. Biol. Res. 382:207–10.

Eckart MR, Dong C, Houghton M, D’Urso N, Ponzetto A. (1993) The effects of using recombinant vaccinia viruses expressing either large or small HDAg to protect woodchuck hepadnavirus carriers from HDV superinfection. Prog. Clin. Biol. Res. 382:201–05.

Nisini R, Paroli M, Accapezzato D, Bonino F, Rosina F, Santantonio T, Sallusto F, Amoroso A, Houghton M, Barnaba V. (1997) Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles. J. Virol. 71:2241–51.

Non-A, Non-B Hepatitis / Hepatitis C Virus

Choo Q-L, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 244:359–62.

Kuo G, Choo Q-L, Alter HJ, Gitnick GI, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, Tegtmeier GE, Bonino F, Colombo M, Lee W-S, Kuo C, Berger K, Shuster JR, Overby LR, Bradley DW, Houghton M. (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 244:362–64.

Esteban JI, Viladomiu L, Bonzalez A, Roget M, Genesca J, Guardia J, Esteban R, Lopez-Talavera JC, Hernandez JM, Vargas V, Buti M, Kuo G, Choo Q-L, Houghton M. (1989) Hepatitis C virus antibodies among risk groups in Spain. Lancet. 334:294–7.

Van Der Poel CL, Ressink HW, Lelie PN, Leentvaar-Kuypers A, Choo Q-L, Kuo G, Houghton M. (1989) Anti-hepatitis C antibodies and non-A, non-B post-transfusion hepatitis in the Netherlands. Lancet. 334:297–8.

Parker T, de Medina M, Jeffers L, Reddy R, Bradley D, Schiff E, Houghton M, Choo Q-L, Kuo G. (1989) Hepatitis C virus HCV: A causative agent of cryptogenic cirrhosis CC among Cubans. Hepatology. 10:685.

Saracco G, Houghton M, Kuo G, Choo Q-L, Rosina F, Lattore V, Torrani Cerenzia MR, Chiandussi L, Bonino F, Rizzetto M. (1989) Anti-hepatitis C virus in non-A non-B patients responding and non-responding to alpha 2A interferon. J. Hepatol. 9:S219. Supplement 1.

Colombo M, Kuo G, Choo QL, Donato MF, Del Ninno E, Tommasini MA, Dioguardi N, Houghton M. (1989) Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet. 334:1006–8.

Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo Q-L, Kuo G. (1989) Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N. Engl. J. Med. 321:1494–1500.

Takeuchi K, Boonmar S, Katayama T, Choo QL, Kuo G, Weiner AJ, Bradley DW, Houghton M, Saito I, Miyamura T. A cDNA fragment of hepatitis C virus isolated from an implicated donor of post-transfusion non-A, non-B hepatitis in Japan. Nucl. Acids Res. 17:10367–72.

Miyamura T, Saito I, Kubo Y, Takeuchi K, Boonmar S, Katayama T, Kuo G, Choo Q-L, Houghton M. (1989) “Hepatitis C virus complementary DNA clones isolated from a single healthy carrier who was shown to be an implicated donor of post-transfusion non-A, non-B hepatitis” in Proceedings of the International Meeting on Non-A, Non-B Hepatitis, Tokyo (Shikata T, Purcell RH, Uchida T. eds.) Elsevier Science Publishers, Amsterdam.

McHutchison JG, Kuo G, Houghton M, Choo Q-L, Redeker AG. (1989) Autoimmune hepatitis is not associated with antibodies to hepatitis C virus (HCV). Hepatology. 10:701.

Kamitsukasa H, Harada H, Yakura M, Fukuda A, Ohbayashi A, Saito I, Miyamura T, Choo Q-L, Houghton M, Kuo G. (1989) Intrafamilial transmission of hepatitis C virus. Lancet. 2:987. Letter.

Colombo M, Kuo G, Choo Q-L, Houghton M, Donato MF, Tommasini MA, Bargiggia S, Piva A, Del Ninno E, Dioguardi N. (1989) High prevalence of antibody to hepatitis C virus in patients with primary liver carcinoma. Hepatology. 10:700.

Colombo M, Kuo G, Choo Q-L, Houghton M, Tommasini MA, Rumi MG, Dioguardi ML, Donato MF, Del Ninno E. (1989) High prevalence of antibody to hepatitis C virus in patients with hepatocellular carcinoma HCC. J. Hepatol. 9:S20. Supplement 1.

Katkov WN, Cody H, Evans AA, Kuo G, Choo Q-L, Houghton M, Dienstag JL. (1989) The role of hepatitis C virus HCV in chronic liver disease. Hepatology. 10:644.

Katkov WN, Friedman LS, Cody H, Evans AA, Kuo G, Choo Q-L, Houghton M, Huggins CE, Dienstag JL. (1989) Elevated serum alanine aminotransferase ALT in blood donors: The contribution of hepatitis C virus HCV. Hepatology. 10:581.

McHutchison JG, Kuo G, Houghton M, Choo Q-L, Redeker AG. (1989) Circulating antibodies to hepatitis C virus HCV: A study of 160 cases of acute and chronic NANB hepatitis. Hepatology. 10:645.

Jeffers L, de Medina M, Hasan F, Reddy R, Parker T, Silva M, Mendez L, Schiff E, Houghton M, Choo Q-L, Kuo G. (1989) Hepatitis C HCV associated idiopathic chronic hepatitis and cryptogenic cirrhosis. Hepatology. 10:644.

Hasan F, Jeffers L, de Medina M, Reddy R, Parker T, Schiff E, Houghton M, Choo Q-L, Kuo G. (1989) Hepatitis C HCV associated hepatocellular carcinoma. Hepatology. 10:608.

Evans AA, Cody H, Kuo G, Choo Q-L, Houghton M, Katkov WN, Dienstag JL. (1989) Seroepidemiology of hepatitis C virus HCV in selected population. Hepatology. 10:644.

Krawczynski K, Kuo G, Dibisceglie A, Houghton M, Bradley DW. (1989) Bloodborne non-A, non-B hepatitis PT-NANB immunohistochemical identification of disease and hepatitis C virus-associated antigens. Hepatology. 10:580.

De Bisceglie AM, Alter H, Kuo G, Houghton M, Hoofnagle JH (1989) Detection of antibody to hepatitis C virus in patients with various chronic liver diseases.

Hepatology. 10:581.

Prince AM, Brotman B, Huima T, Krauledat P, Houghton M, Kuo G, Kuo Q-L. (1989) “Distinction between chronic and self-limited forms of hepatitis C virus infection” in International Meeting on Non-A, Non-B Hepatitis, Tokyo, Japan (Shikata T, Purcell RH, Uchida T. eds.) pp.7–16. Elsevier Science Publishers, Amsterdam.

Houghton M. (1990) Discovery of hepatitis C virus and assay of non-A, non-B hepatitis virus. Jikken Igaku. 8:203–6.

Mosley JW, Aach RD, Hollinger FB, Stevens CE, Barbosa LH, Nemo GJ, Holland PV, Bancroft WH, Zimmerman HJ, Kuo G, Choo Q-L, Houghton M. (1990) Non-A, non-B hepatitis and antibody to hepatitis C virus. JAMA. 263:77–8.

Weiner AJ, Kuo G, Bradley DW, Bonino F, Saracco G, Lee C, Rosenblatt J, Choo Q-L, Houghton M. (1990) Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet. 335:1–3.

Choo Q-L, Weiner AJ, Overby LR, Kuo G, Houghton M. (1990) Hepatitis C virus: The major causative agent of viral non-A, non-B hepatitis. Br. Med. Bull. 46:423–41.

Miyamura T, Saito I, Katayama T, Kikuchi S, Tateda A, Houghton M, Choo Q-L, Kuo G. (1990) Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: Application to diagnosis and blood screening for posttransfusion hepatitis. Proc. Natl. Acad. Sci. USA. 87:983–7.

Kew MC, Houghton M, Choo Q-L, Kuo G. (1990) Hepatitis C virus antibodies in southern African blacks with hepatocellular carcinoma. Lancet. 335:873–4.

Chien D-S, Kuo GC, Sung J-L, Lai M-Y, Sheu J-C, Chen P-J, Yang P-M, Hsu H-M, Chang M-H, Chen C-J, Hahn L-C, Choo Q-L, Wang T-H, Houghton M. (1990) Hepatitis C virus infection in an area hyperendemic for hepatitis B and chronic liver disease: The Taiwan experience. J. Infect. Dis. 162:817–22.

Makris M, Preston FE, Triger DR, Underwood JCE, Choo Q-L, Kuo G, Houghton M. (1909) Hepatitis C antibody and chronic liver disease in haemophilia. Lancet. 335:1117–9.

Stevens CE, Taylor PE, Pindyck J, Choo Q-L, Bradley DW, Kuo G, Houghton M. (1990) Epidemiology of hepatitis C virus. A preliminary study in volunteer blood donors. JAMA. 263:49–53.

Jeffers L, Perez G, de Medina M, Schiff E, Ortiz-Interian C, Bourgoignie J, Vaamonde CA, Houghton M, Choo Q-L, Kuo G. (1990) Hepatitis C HCV infection in hemodialysis units. Kidney Int. 37:303.

Oliveri F, Baldi M, Brunetto MR, Saracco G, Rosina F, Cerenzia MT, Rizzetto M, Soranzo ML, Colla L, Vallauri P, Verme G, Kuo G, Houghton M, Bonino F. (1990) Antibody to hepatitis C virus in the serum of patients with chronic hepatitis. Eur. J. Gastroenterol. Hepatol. 2:347–50.

Houghton M, Richman K, Han J, Berger K, Lee C, Dong C, Overby L, Weiner A, Bradley D, Kuo G, Choo Q-L. (1990) “Hepatitis C virus (HCV): A relative of the pestiviruses and flaviviruses” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 328–33. Williams & Wilkins, Baltimore, MD.

Choo Q-L, Berger K, Kuo G, Houghton M. (1990) “Detection and mapping of immunologic epitopes expressed by bacterial cDNA clones of the hepatitis C virus” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 345–6. Williams & Wilkins, Baltimore, MD.

Kuo G, Choo Q-L, Shuster J, Kuo C, Berger K, Lee WS, Medina-Selby A, Houghton M. (1990) “Serodiagnosis of hepatitis C viral infection using recombinant-based assays for circulating antibodies to different viral proteins” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 347–9. Williams & Wilkins, Baltimore, MD.

Weiner AJ, Truett MA, Rosenblatt J, Han J, Quan S, Polito AJ, Kuo G, Choo Q-L, Houghton M. (1990) “HCV: Immunologic and hybridization-based diagnostics” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 360–3. Williams & Wilkins, Baltimore, MD.

Boonmar S., Takeuchi K, Kubo Y, Katayama T, Harada H, Ohbayashi A, Choo Q-L, Kuo G, Houghton M, Saito I, Miyamura T. (1990) “Molecular cloning of hepatitis C virus cDNA from plasma of an implicated donor or post-transfusion non-A, non-B hepatitis” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 371–4. Williams & Wilkins, Baltimore, MD.

Shimizu YK, Weiner AJ, Rosenblatt J, Wong DC, Shapiro M, Popkin T, Houghton M, Alter HJ, Purcell RH. (1990) Early events in hepatitis C virus infection of chimpanzees. Proc. Natl. Acad. Sci. USA. 87:6441–4.

Van der Poel CL, Reesink HW, Lelie PN, Cuijpers MT, Leentvaar,-Kuypers A, Bakker E, Exel-Oehlers PJ, Polito A, Houghton M, Schaasberg W. (1990) “Impact of blood-donor screening for anti-HCV versus ALT, and cofactors for infectivity of anti-HCV-positive blood” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 427–30. Williams & Wilkins, Baltimore, MD.

Esteban JI, González A, Hernández JM, Madoz P, Muniz E, Torras J, Enriquez J, Buenestado J, Martin-Vega C, Sánchez C, Esteban R, Guardia J, Houghton M, Alter HJ. (1990) “Open prospective efficacy trial of anti-HCV screening of blood donors to prevent posttransfusion hepatitis: Interim report of the Barcelona PTH study” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 431–3. Williams & Wilkins, Baltimore, MD. Krawczynski K, Kuo G, Dibisceglie A, Bradley D, Houghton M, Alter M, Ebert J. (1990) “Blood-borne non-A, non-B hepatitis: Detection and identification of hepatitis C virus and disease-associated antigen HCV Ag in hepatocytes” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 434–5. Williams & Wilkins, Baltimore, MD.

Prince AM, Brotman B, Huima T, Krauledat P, Houghton M, Kuo G, Choo Q-L, Polito A, Di Nello R, Nelles MJ. (1990) Use of anti-HCV determinations for diagnosis of chronic HCV infection” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 450–5. Williams & Wilkins, Baltimore, MD.

Miyamura T, Saito I, Yoneyama T, Takeuchi K, Ohbayashi A, Watanabe Y, Choo Q-L, Houghton M, Kuo G. (1990) ‘Role of hepatitis C virus in hepatocellular carcinoma” in Viral Hepatitis and Liver Disease (Hollinger FB, Lemon SM, Margolis HS. eds.) pp. 559–62. Williams & Wilkins, Baltimore, MD.

Takeuchi K, Boonmar S, Kubo Y, Katayama T, Harada H, Ohbayashi A, Choo Q-L, Kuo G, Houghton M, Saito I, Miyamura T. (1990) Hepatitis C viral cDNA clones isolated from a healthy carrier donor implicated in post-transfusion non-A, non-B hepatitis. Gene. 91:287–91.

Watanabe J, Minegishi K, Mitsumori T, Ishifuji M, Oguchi T, Ueda M, Tokunaga E, Tanaka E, Kiyosawa K, Furuta S, Katayama T, Kuo G, Choo Q-L, Houghton M, Nishioka K. (1990) Prevalence of anti-HCV antibody in blood donors in the Tokyo area. Vox Sang. 59:86–8.

Katayama T, Kikuchi S, Tanaka Y, Saito I, Miyamura T, Choo Q-L, Houghton M, Kuo G. (1990) Blood screening for non-A, non-B hepatitis by hepatitis C virus antibody assay. Transfusion. 30:374–6.

Takeuchi K, Kubo Y, Boonmar S, Watanabe Y, Katayama T, Choo Q-L, Kuo G, Houghton M, Saito I, Miyamura T. (1990) The putative nucleocapsid and envelope protein genes of hepatitis C virus determined by comparison of the nucleotide sequences of two isolates derived from an experimentally infected chimpanzee and healthy human carriers. J. Gen. Virol. 71:3027–33.

Kremsdorf D, Thiers V, Garreau F, Duclos H, Porchon C, Houghton M, Tiollais P, Brechot C. (1990) Cloning and sequence analysis of hepatitis B virus variants in non-A and non-B infections. J. Hepatol. 11:S36. Supplement 2.

Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S, Watanabe Y, Koi S, Onji M, Ohta Y, Choo Q-L, Houghton M, Kuo G. (1990) Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA. 87:6547–9.

Hasan F, Jeffers LJ, De Medina M, Reddy KR, Parker T, Schiff ER, Houghton M, Choo Q-L, Kuo G. (1990) Hepatitis C-associated hepatocellular carcinoma. Hepatology. 12:589–91.

Takeuchi K, Kubo Y, Boonmar S, Watanabe Y, Katayama T, Choo Q-L, Kuo G, Houghton M, Saito I, Miyamura T. (1990) Nucleotide sequence of core and envelope genes of the hepatitis C virus genome derived directly from human healthy carriers. Nuc. Acids Res. 18:4626.

Weiner AJ, Truett MA, Han J, Polito AJ, Choo, Q-L, Rosenblatt J, Quan S, Kuo G, Houghton M, Page E, Agius C, Nelles MJ. (1990) HCV testing in low-risk population. Lancet. 336:695. Letter.

Makris M, Dewar MS, Preston FE, Choo Q-L, Kuo G, Houghton M. (1990) The relation of hepatitis C antibodies to acute non-A, non-B hepatitis NANBH in previously untreated hemophilic patients. Br. J. Haematol. 74:44. Supplement 1.

Magrin S, Craxi A, Almasio P, Fabiano C, Fiorentino G, Palazzo U, Pinzello GB, Provenzano G, Pagliaro L, Houghton M, Han JH. (1990) HCV infection in autoimmune chronic active hepatitis. J. Hepatol. 11:S99. Supplement 2.

Thaler MM, Landers DW, Wara DW, Houghton M, Veereman-Wauters G, Sweet RL, Brauer M, Han JH. (1990) Vertical transmission of hepatitis C virus detected by the polymerase chain reaction. Hepatology. 12:849.

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Nishioka K, Watanabe J, Furuta S, Tanaka E, Iino S, Suzuki H, Tsuji T, Yano M, Kuo G, Choo Q-L, Houghton M, Oda T. (1991) A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan. Cancer. 67:429–33.

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Choo Q-L, Richman KH, Han JH, Berger K, Lee C, Dong C, Gallegos C, Coit D, Medina-Selby A, Barr PJ, Weiner AJ, Bradley DW, Kuo G, Houghton M. (1991) Genetic organization and diversity of the hepatitis C virus. Proc. Natl. Acad. Sci. USA. 88:2451–5.

Weiner AJ, Brauer MJ, Rosenblatt J, Richman KH, Tung J, Crawford K, Bonino F, Saracco G, Choo Q-L, Houghton M, Han JH. (1991) Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology. 180:842–8.

van der Poel CL, Cuypers HTM, Reesink HW, Weiner AJ, Quan S, DiNello R, van Boven JJP, Winkel I, Mulder-Folkerts D, Exel-Oehlers PJ, Schaasberg W, Leentvaar-Kuypers A, Polito A, Houghton M, Lelie PN. (1991) Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. Lancet. 337:317–9.

Reesink HW, Van der Poel CL, Plaisier ADD, Verstraten JW, Cuypers M. (1991) Comparison of first and second generation anti-HCV recombinant immunoblot assay with 5’ UTR PCR. Transfusion. 31:57S.

Han JH, Shyamala V, Richman KH, Brauer MJ, Irvine B, Urdea MS, Tekamp-Olson P, Kuo G, Choo Q-L, Houghton M. (1991) Characterization of the terminal regions of hepatitis C viral RNA: Identification of conserved sequences in the 5’ untranslated region and poly(A) tails at the 3’end. Proc. Natl. Acad. Sci. USA. 88:1711–5.

Magrin S, Craxi A, Fabiano C, Fiorentino G, Almasio P, Palazzo U, Pinzello G, Provenzano G, Pagliaro L, Choo Q-L, Kuo G, Polito A, Han J, Houghton M. (1991) Hepatitis C virus replication in ‘autoimmune’ chronic hepatitis. J. Hepatol. 13:364–7.

Cha T-A, Kolberg J, Irvine B, Stempien M, Beall E, Yano M, Choo Q-L, Houghton M, Kuo G, Han JH, Urdea MS. (1991) Use of a signature nucleotide sequence of Hepatitis C virus for detection of viral RNA in human serum and plasma. J. Clin. Microbiol. 29:2528–34.

Houghton M. (1991) “Molecular virology of HCV” in Report on the Proceedings, Second International Symposium on HCV, Los Angeles (Bradley DW. ed.) pp.2–3. Advanced Therapeutics Communications, Secaucus, New Jersey.

Krawczynski K, Beach M, Mimms L, Meeks E, Vallari D, Taskar S, Kuo G, Houghton M, Bradley D. (1991) Replication and antigenic expression of HCV antiviral antibody response and liver pathology in acute and chronic HCV infection. Hepatology. 14:78A.

Houghton M, Weiner A, Han J, Kuo G, Choo Q-L. (1991) Molecular biology of the hepatitis C viruses: Implications for diagnosis, development and control of viral disease. Hepatology. 14:381–8.

Colombo M, Rumi MG, Donato MF, Tommasini MA, Del Ninno E, Ronchi G, Kuo G, Houghton M. (1991) Hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma. Dig. Dis. Sci. 36:1130–3.

Thudium K, Spaete R, Berger K, Choo Q-L, Houghton M, Ralston R. (1991) Expression and characterization of HCV structural proteins using in-vitro translation and recombinant vaccinia viruses. J. Cell. Biochem. 47:92. Supplement 15E.

McHutchison JG, Kuo G, Houghton M, Choo Q-L, Redeker AG. (1991) Hepatitis C virus antibodies in acute icteric and chronic non-A, non-B hepatitis. Gastroenterology. 101:1117–9.

Saracco G, Baldi M, Calvo PL, Manzini P, Abate M, Chiaberge E, Brunetto MR, Rizzetto M, Chien D, Kuo G, Houghton M, Bonino F. (1991) Hepatitis C virus markers for monitoring interferon therapy in chronic hepatitis C. Hepatology. 14:75A.

Cuypers HT, Winkel IN, van der Poel CL, Reesink HW, Lelie PN, Houghton M, Weiner A. (1991) Analysis of genomic variability of hepatitis C virus. J. Hepatol. 13:S15–9.

Rosina F, Fabiano A, Garripoli A, Smedile A, Mattalia A, Eckart MR, Houghton M, Bonino F. (1991) Rabbit-derived anti-HD antibodies for HDAg immunoblotting. J. Hepatol. 13:130–3.

Weiner AJ, Christopherson C, Hall JE, Bonino F, Saracco G, Crawford K, Marion CD, Crawford KA, Venkatakrishna S, Miyamura T, McHutchinson J, Cuypers T, Houghton M. (1991) Sequence variation in hepatitis C viral isolates. Hepatology. 13:S6–14.

Krawczynski K, Beach MJ, Bradley DW, Kuo G, di Bisceglie AM, Houghton M, Reyes GR, Kim JP, Choo Q-L, Alter MJ (1992) Hepatitis C virus antigen in hepatocytes: Immunomorphologic detection and identification. Gastroenterology. 103:622–9.

Bresters D, Mauser-Bunschoten EP, Cuypers HT, Lelie PN, Han JH, Jansen PL, Houghton M, Reesink HW (1992) Disappearance of hepatitis C virus RNA in plasma during interferon alpha-2B treatment in hemophilia patients. Scand. J. Gastroenterol. 27:166–8.

Bresters D, Cuypers HT, Reesink HW, Schaasberg WP, van der Poel CL, Mauser-Bunschoten EP, Houghton M, Choo Q-L, Kuo G, Lesniewski R, Troonen H, Lelie PN. (1992) Enhanced sensitivity of a second generation ELISA for antibody to hepatitis C virus. Vox Sang. 62:213–7.

Overby LR, Houghton M. (1992) “Hepatitis viruses” in Laboratory Diagnosis of Viral Infections (Lennette EH. ed.) pp. 403–44. Marcel Dekker, New York.

Spaete RR, Alexander DA, Rugroden ME, Choo Q-L, Berger K, Crawford K, Kuo C, Leng S, Lee C, Ralston R, Thudium K, Tung JW, Kuo G, Houghton M. (1992) Characterization of the hepatitis C virus E2/NS1 gene product expressed in mam-malian cells. Virology. 188:819–30.

Weiner AJ, Geysen HM, Christopherson C, Hall JE, Mason TJ, Saracco G, Bonino F, Crawford K, Marion CD, Crawford KA, Brunetto M, Barr PJ, Miyamura T, McHutchinson J, Houghton M. (1992) Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: Potential role in chronic HCV infections. Proc. Natl. Acad. Sci. USA. 89:3468–72.

Houghton M. (1992) “Heterogeneity of the HCV genome: Importance for control of the disease” in Hepatitis C Virus: Scientific and Clinical Status (Deinhardt F, Bradley DW, Houghton M. eds.) pp. 8–9. Advanced Therapeutics Communications, Secaucus, New Jersey.

Jeffers LJ, Hasan F, De Medina M, Reddy R, Parker T, Silva M, Mendez L, Schiff ER, Manns M, Houghton M. (1992) Prevalence of antibodies to hepatitis C virus among patients with cryptogenic chronic hepatitis and cirrhosis. Hepatology. 15:187–90.

Weiner AJ, Christopherson C, Hall JE, Crawford K, Marion CD, Crawford KA, Barr PJ, Richman K, Kuo G, Houghton M. (1992) “The hypervariable amino terminus of the hepatitis C virus E2/NS1 protein appears to be under immune selection” in Vaccines 92 (Brown F, Chanock RM, Ginsberg HS, Lerner RA. eds.) pp. 303–8. Cold Spring Harbor Laboratory Press, New York.

Chien DY, Choo Q-L, Tabrizi A, Kuo C, McFarland J, Berger K, Lee C, Shuster R, Nguyen T, Moyer DL, Tong M, Furuta S, Omata M, Alter H, Schiff E, Jeffers L, Houghton M, Kuo G. (1992) Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: Re-evaluation of the role of HCV in liver disease. Proc. Natl. Acad. Sci. USA. 89:10011–5.

Choo Q-L, Kuo G, Weiner A, Wang K-S, Overby L, Bradley D, Houghton M. (1992) Identification of the major, parenteral non-A, non-B hepatitis agent (hepatitis C virus) using a recombinant cDNA approach. Sem. Liver Dis. 12:279–88.

Cuypers HT, Bresters D, Winkel IN, Reesink HW Weiner AJ, Houghton M, van der Poel CL, Lelie PN. (1992) Storage conditions of blood samples and primer selection affect the yield of cDNA polymerase chain reaction products of hepatitis C virus. J. Clin. Microbiol. 30:3220–4.

Weiner AJ, Venkatakrishna S, Hall JE, Houghton M, Han J. (1992) “PCR: Application to hepatitis C virus (HCV) research and diagnostics” in Frontiers in Virology (Becker Y, Darai G. eds.) pp. 86–100. Springer Verlag, New York.

Van der Poel CL, Bresters D, Reesink HW, Plaisier AAD, Schaasberg W, Leentvaar-Kuypers A, Choo Q-L, Quan S, Polito A, Houghton M, Kuo G, Lelie PN, Cuypers HTM. (1992) Early antihepatitis-C virus response with second generation C200/C22 ELISA. Vox Sang. 62:208–12.

Han JH, Houghton M. (1992) Group specific sequences and conserved secondary structures at the 3’ end of HCV genome and its implication for viral replication. Nucl. Acids Res. 20:3520.

Koziel MJ, Dudley D, Wong JT, Dienstag J, Houghton M, Ralston R, Walker B. (1992) Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J. Immunol. 149:3339–44.

Yoo BJ, Spaete RR, Geballe AP, Selby M, Houghton M, Han JH. (1992) 5’ end-dependent translation initiation of hepatitis C viral RNA and the presence of putative positive and negative translational control elements within the 5’ untranslated region. Virology. 191:889–99.

Botarelli P, Brunetto MR, Weiner AJ, Minutello MA, Unutmaz D, Calvo P, Bonino F, Houghton M, Abrignani S. (1993) T cell response to recombinant proteins of hepatitis C virus in blood and liver of patients with different clinical courses of infection. Gastroenterology. 104:580–7.

Chien DY, Choo Q-L, Tabrizi A, Kuo C, McFarland J, Berger K, Lee C, Shuster JR, Nguyen T, Moyer DL, Tong M, Furuta S, Omata M, Fong CT, Tegtmeier G, Alter H, Schiff E, Jeffers L, Houghton M, Kuo G. (1993) Use of recombinant HCV antigen in the serodiagnosis of hepatitis C virus infection: Significant improvement in HCV antibody detection as compared with the first generation HCV C100-3 ELISA and the synthetic peptide EIA tests. J. Gastroenterol. Hepatol. 8:S33–9.

Eckart MR, Selby M, Masiarz F, Lee C, Berger K, Crawford K, Kuo C, Kuo G, Houghton M. (1993) The hepatitis C virus encodes a serine protease involved in processing of the putative nonstructural proteins from the viral polyprotein precursor. Biochem. Biophys. Res. Comm. 192:399–406.

Saracco G, Rosina F, Abate ML, Chiandussi L, Gallo V, Cerutti E, Di Napoli A, Solinas A, DePlano A, Tocco A, Cossu P, Chien D, Kuo G, Polito A, Weiner AJ, Houghton M, Verme G, Bonino F, Rizzetto M (1993) Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-α2b. Hepatology. 18:1300–5.

Koziel MJ, Dudley D, Afdhal N, Choo Q-L, Houghton M, Ralston R, Walker BD. (1993) Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognized epitopes in the core and envelope proteins of HCV. J. Virol. 67:7522–32.

Bresters D, Mauser-Bunschoten EP, Cuypers HT, Han JH, Jansen PL, Chamuleau RA, Houghton M, Reesink HW. (1993) Long term treatment of chronic hepatitis C with interferon alfa-2b: disappearance of HCV-RNA in a pilot study of eight haemophilia patients. Gut (England). 34:S124–5.

Rosina F, Fabiano A, Maran E, Cozzolongo R, Smedile A, Mazzucco G, Garripoli A, Costa C, Eckart MR, Houghton M. (1993) Rabbit-derived anti-HD antibodies for HDAg immunoblotting. Proc. Clin. Biol. Res. 382:189–91.

Selby MJ, Choo Q-L, Berger K, Kuo G, Glazer E, Eckart M, Lee C, Chien D, Kuo C, Houghton M. (1993) Expression, identification and subcellular localization of the proteinsencoded by the hepatitis C viral genome. J. Gen. Virol. 4:1103–13.

Weiner AJ, Thaler MM, Crawford K, Ching K, Kansopon J, Chien DY, Hall JE, Hu F, Houghton M. (1993) A unique, predominant hepatitis C virus variant found in an infant born to a mother with multiple variants. J. Virol. 67:4365–8.

Minutello MA, Pileri P, Unutmaz D, Censini S, Kuo G, Houghton M, Brunetto MR, Bonino F, Abrignani S. (1993) Compartmentalization of T lymphocytes to the site of disease: Intrahepatic CD4+ T cells specific for the protein NS4 of hepatitis C virus in patients with chronic hepatitis C. J. Exp. Med. 178:17–25.

Lok ASF, Chien D, Choo Q-L, Chan T-M, Chiu EKW, Cheng IKP, Houghton M, Kuo G. (1993) Antibody response to core, envelope and nonstructural hepatitis C virus antigens: Comparison of Immunocompetent and immunosuppressed patients. Hepatology. 18:497–502.

Chien DY, Choo Q-L, Ralston R, Spaete R, Tong M, Houghton M, Kuo G. (1993) Persistence of HCV despite antibodies to both putative envelope glycoprotein. Lancet. 342:933. Letter.

Erickson AL, Houghton M, Choo Q-L, Weiner AJ, Ralston R, Muchmore E, Walker CM. (1993) Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C. J. Immunol. 151:4189–99.

Ralston R, Thudium K, Berger K, Kuo C, Gervase B, Hall J, Selby M, Kuo G, Houghton M, Choo Q-L. (1993) Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses. J. Virol. 67:6753–61.

Botarelli P, Brunetto MR, Minutello MA, Calvo P, Unutmaz D, Weiner AJ, Choo Q-L, Shuster JR, Kuo G, Bonino F, Houghton M, Abrignani S. (1993) T-lymphocyte response to hepatitis C virus in different clinical courses of infection. Gastroenterology. 104:580–7.

Choo Q-L, Kuo G, Ralston R, Weiner A, Chien D, Van Nest G, Han J, Berger K, Thudium K, Kuo C, Kansopon J, McFarland J, Tabrizi A, Ching K, Moss B, Cummins LB, Houghton M, Muchmore E. (1994) Vaccination of chimpanzees against infection by the hepatitis C virus. Proc. Natl. Acad. Sci. USA. 91:1294–8.

Simmonds P, Alfredo A, Alter HJ, Bonino F, Bradley DW, Brechot C, Brouwer JT, Chan S-W, Chayama K, Chen D-S, Choo Q-L, Colombo M, Cuypers HTM, Date T, Dusheiko GM, Esteban JI, Fay O, Hadziyannis SJ, Han J, Hatzakis A, Holmes EC, Hotta H, Houghton M, Irvine B, Kohara M, Kolberg JA, Kuo G, Lau JYN, Lelie PN, Maertens G, McOmish F, Miyamura T, Mizokami M, Nomoto A, Prince AM, Reesink HW, Rice C, Roggendorf M, Schalm SW, Shimotohno K, Stuyver L, Trépo C, Weiner A, Yap PL, Urdea MS. (1994) A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology. 19:1321–4.

Houghton M, Selby M, Weiner A, Choo Q-L. (1994) Hepatitis C virus: Structure, protein products and processing of the polyprotein precursor. Curr. Stud. Hematol. Blood Trans. 61:1–11.

Houghton M, Choo Q-L, Kuo G, Ralston R, Selby M, Weiner A, Chien D, Han J, Walker C, Abrignani S, Koziel M, Walker B, Cummins L, Muchmore E. (1994) “The hepatitis C virus: Genetic organization, persistence, and vaccine strategies” in Viral Hepatitis and Liver Disease (Nishioka K, Suzuki H, Mishiro S, Oda T. eds.) pp. 33–7. Springer-Verlag, Tokyo.

Weiner AJ, Thaler MM, Crawford K, Kansopon J, Ching K, Hall JE, Hu F, Chien D, Houghton M. (1994) “HCV-positive, HIV-1-negative mothers transmit HCV” in Viral Hepatitis and Liver Disease (Nishioka K, Suzuki H, Mishiro S, Oda T. eds.) pp. 463–7. Springer-Verlag, Tokyo.

Ray R, Khanna A, Lagging LM, Meyer K, Choo Q-L, Ralston R, Houghton M, Becherer PR. (1994) Peptide immunogen mimicry of putative E1 glycoprotein-specific epitopes in hepatitis C virus. J. Virol. 68:4420–6.

Selby MJ, Glazer E, Masiarz F, Houghton M. (1994) Complex processing and protein: Protein interactions in the E2:NS2 region of HCV. Virology. 204:114–22.

Saracco G, Abate ML, Baldi M, Calvo PL, Manzini P, Brunetto MR, Oliveri F, Kuo G, Chien D, Houghton M, Verme G, Rizzetto M, Bonino F. (1994) Hepatitis C virus markers in patients with long-term biochemical and histological remission of chronic hepatitis. Liver. 14:65–70.

Chien DY, McFarland J, Tabrizi A, Kuo C, Houghton M, Kuo G. (1994) “Distinct subtypes of hepatitis C virus defined by antibodies directed to the putative core, NS4, and NS5 region polypeptides” in Viral Hepatitis and Liver Disease (Nishioka K, Suzuki H, Mishiro S, Oda T. eds.) pp. 320–4. Springer-Verlag, Tokyo.

Yoo BJ, Selby MJ, Choe J, Suh BS, Choi SH, Joh JS, Nuovo GJ, Lee H-S, Houghton M, Han JH. (1995) Transfection of a differentiated human hepatoma cell line (Huh7) with in vitro-transcribed hepatitis C virus (HCV) RNA and establishment of a long-term culture persistently infected with HCV. J. Virol. 69:32–8.

Cerny A, McHutchison JG, Pasquinelli C, Brown ME, Brothers MA, Grabscheid B, Fowler P, Houghton M, Chisari FV. (1995) Cytotoxic T lymphocyte response to hepatitis C virus – derived peptides containing the HLA A2.1 binding motif. J. Clin. Invest. 95:521–30.

Weiner A, Erickson AL, Kansopon J, Crawford K, Muchmore E, Hughes AL, Houghton M, Walker CM (1995) Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant. Proc. Natl. Acad. Sci. USA. 92:2755–9.

Cerny A, Fowler P, Brothers MA, Houghton M, Schlicht HJ, Chisari FV. (1995) Induction in vitro of a primary human antiviral cytotoxic T cell response. Eur. J. Immunol. 25:627–30.

Houghton M, Choo Q-L, Kuo G, Weiner A, Chien D, Ralston R, Urdea M, Moss B, Purcell R, Cummins L, Muchmore E. (1995) Prospects for prophylactic and therapeutic hepatitis C virus vaccines. Princess Takamatsu Symp. 25:237–43.

Weiner AJ, Erickson AL, Kansopon J, Crawford K, Muchmore E, Houghton M, Walker CM. (1995) Association of cytotoxic T lymphocyte (CTL) escape mutations with persistent hepatitis C virus (HCV) infection. Princess Takamatsu Symp. 25:227–35.

Lagging LM, Meyer K, Hoft D, Houghton M, Belshe RB, Ray R. (1995) Immune responses to plasmid DNA encoding the hepatitis C virus core protein. J. Virol. 69:5859–63.

Koziel MJ, Dudley D, Afdhal N, Grakoui A, Rice C, Choo Q-L, Houghton M, Walker BD. (1995) HLA class I-restricted cytotoxic T lymphocytes specific for hepatitis C virus: Identification of multiple epitopes and characterization of patterns of cytokine release. J. Clin. Invest. 96:2311–21.

Piazza M, Chien D, Quan S, Houghton M. (1996) Lack of antibodies to the envelope glycoproteins of hepatitis C virus in immunoglobulin preparations from screened donors. Boll. Soc. Ital. Biol. Sper. 72:69–70.

Houghton M. (1996) “Hepatitis C viruses” in Fields Virology (Fields BN, Knipe DM, Howley PM et al. eds.) pp. 1035–58. Lippincott-Raven Publishers, Philadelphia.

Rosa D, Campagnoli S, Moretto C, Guenzi E, Cousens L, Chin M, Dong C, Weiner AJ, Lau JY, Choo Q-L, Chien D, Pileri P, Houghton M, Abrignani S. (1996) A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. Proc. Natl. Acad. Sci. USA. 93:1759–63.

Missale G, Bertoni R, Lamonaca V, Valli A, Massari M, Mori C, Rumi MG, Houghton M, Fiaccadori F, Ferrari C. (1996) Different clinical behaviors of acute hepatitis virus infection are associated with different vigor of the anti-viral cell-mediated immune response. J. Clin. Invest. 98:706–14.

Rehermann B, Chang KM, McHutchinson JG, Kokka R, Houghton M, Chisari FV. (1996) Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection. J. Clin. Invest. 98:1432–40.

Rehermann B, Chang KM, McHutchinson J, Kokka R, Houghton M, Rice CM, Chisari FV. (1996) Differential cytotoxic T-lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. J. Virol. 70:7092–102.

Houghton M, Choo Q-L, Chien D, Kuo G, Weiner A, Coates S, Cousens L, Wininger M, Selby M, Ralston R, Berger K, Dong C, Crawford K, Kansopon J, Chin M, Wong S, Tabrizi-Weight A, Purcell RH, Muchmore E, Morandi M, Rosa D, Abrignani S. (1996) “Development of an HCV vaccine” in Viral Hepatitis and Liver Disease (Rizzetto M, Purcell RH, Gerin JL, Verme G. eds.) pp. 656–9. Edizioni Minerva Medica, Torino, Italy.

Nelson DR, Marousis CG, Davis GL, Rice CM, Wong J, Houghton M, Lau YN (1997) The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C. J. Immunol. 158:1473–81.

Pasquinelli C, Shoenberger JM, Chung J, Chang KM, Guidotti LG, Selby M, Berger K, Lesniewski R, Houghton M, Chisari FV. Hepatitis C virus core and E2 protein expression in transgenic mice. Hepatology. 25:719–27.

Diepolder HM, Gerlach J-T, Zachoval R, Hoffmann RM, Jung M-C, Wierenga EA, Scholz S, Santantonio T, Houghton M, Southwood S, Sette A, Pape GR. (1997) Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection. J. Virol. 71:6011–9.

Calvo PL, Kansopon J, Sra K, Quan S, DiNello R, Guaschino R, Calabrese G, Danielle F, Brunetto, Bonino F, Massaro AL, Polito A, Houghton M, Weiner AJ. (1998) Hepatitis C virus heteroduplex tracking assay for genotype determination reveals diverging genotype 2 isolates in Italian hemodialysis patients. J. Clin. Microbiol. 36:227–33.

Wong DKH, Dudley DD, Afdhal NH, Dienstag J, Rice CM. (1998) Liver-derived CTL in hepatitis C virus infection: Breadth and specificity of responses in a cohort of persons with chronic infection. J. Immunol. 160:1479–88.

Ishii K, Rosa D, Watanabe Y, Katayama T, Harada H, Wyatt C, Kiyosawa K, Aizaki H, Matsuura Y, Houghton M, Abrignani S, Miyamura T. (1998) High titers of antibodies inhibiting the binding of envelope to human cells correlate with natural resolution of chronic hepatitis C. Hepatology. 28:1117–20.

Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G, Abrignani S. (1998) Binding of hepatitis C virus to CD81. Science. 282:938–41.

Selby M, Erickson A, Dong C, Cooper S, Parham P, Houghton M, Walker CM. (1999) Hepatitis C virus envelope glycoprotein E1 originates in the endoplasmic reticulum and requires cytoplasmic processing for presentation by class I MHC molecules. J. Immunol. 162:669–76.

Cooper S, Erickson AL, Adams EJ, Kansopon J, Weiner AJ, Chien DY, Houghton M, Parham P, Walker CM. (1999) Analysis of a successful immune response against hepatitis C virus. Immunity. 10:439–49.

Colombatto P, Brunetto MR, Kansopon J, Oliveri F, Maina A, Aragon U, Bortoli ML, Scatena F, Baicchi U, Houghton M, Bonino F, Weiner AJ. (1999) High prevalence of G1 and G2 TT-virus infection in subjects with high and low blood exposure risk: identification of G4 isolates in Italy. J. Hepatol. 31:990–6.

Abrignani S, Houghton M, Hsu HH. (1999) Perspectives for a vaccine against hepatitis C virus. J. Hepatol. 31 Suppl 1:259–63.

Hsu HH, Abrignani S, Houghton M. (1999) Prospects for a hepatitis C virus vaccine. Clin. Liver Dis. 3:901–15.

Liberman E, Fong YL, Selby MJ, Choo QL, Cousens L, Houghton M, Yen TS. (1999) Activation of the grp78 and grp94 promoters by hepatitis C virus E2 envelope protein. J. Virol. 73:3718–22.

Mustilli AC, Izzo E, Houghton M, Galeotti CL. (1999) Comparison of secretion of a hepatitis C virus glycoprotein in Saccharomyces cerevisiae and Kluyveromyces lactis. Res. Microbiol. 150:179–87.

Rosen HR, Hinrichs DJ, Gretch DR, Koziel MJ, Chou S, Houghton M, Rabkin J, Corless CL, Bouwer HG. (1999) Association of multispecific CD4(+) response to hepatitis C and severity of recurrence after liver transplantation. Gastroenterology. 117:926–32.

Allander T, Drakenberg K, Beyene A, Rosa D, Abrignani S, Houghton M, Widell A, Grillner L, Persson MA. (2000) Recombinant human monoclonal antibodies against different conformational epitopes of the E2 envelope glycoprotein of hepatitis C virus that inhibit its interaction with CD81. J. Gen. Virol. 81:2451–9.

Alter HJ, Houghton M. (2000) Clinical Medical Research Award. Hepatitis C virus and eliminating post-transfusion hepatitis. Nat. Med. 6:1082–6.

Fan XG, Tang FQ, Yi H, Liu WE, Houghton M, Hu GL. (2000) Effect of IL-12 on T-cell immune responses in patients with chronic HCV infection. APMIS. 108:531–8.

Heile JM, Fong YL, Rosa D, Berger K, Saletti G, Campagnoli S, Bensi G, Capo S, Coates S, Crawford K, Dong C, Wininger M, Baker G, Cousens L, Chien D, Ng P, Archangel P, Grandi G, Houghton M, Abrignani S. (2000) Evaluation of hepatitis C virus glycoprotein E2 for vaccine design: an endoplasmic reticulum-retained recombinant protein is superior to secreted recombinant protein and DNA-based vaccine candidates. J. Virol. 74:6885–92.

Houghton M. (2000) Strategies and prospects for vaccination against the hepatitis C viruses. Curr. Top. Microbiol. Immunol. 242:327–39. Review.

Lee AY, Manning WC, Arian CL, Polakos NK, Barajas JL, Ulmer JB, Houghton M, Paliard X. (2000) Priming of hepatitis C virus-specific cytotoxic T lymphocytes in mice following portal vein injection of a liver-specific plasmid DNA. Hepatology. 31:1327–33.

Lee AY, Polakos NK, Otten GR, Ulmer JB, Houghton M, Paliard X. (2000) Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization. Vaccine. 18:1962–8.

Petracca R, Falugi F, Galli G, Norais N, Rosa D, Campagnoli S, Burgio V, Di Stasio E, Giardina B, Houghton M, Abrignani S, Grandi G. (2000) Structure-function analysis of hepatitis C virus envelope-CD81 binding. J. Virol. 74:4824–30.

Weiner A, Chien D, Choo Q-L, Coates S, Kuo G, Houghton M. (2000) “Humoral response to HCV” in Hepatitis C. (Liang J, Hoofnagle J. eds.), pp. 125–145. Academic Press.

Schirren CA, Jung MC, Gerlach JT, Worzfeld T, Baretton G, Mamin M, Hubert Gruener N, Houghton M, Pape GR. (2000) Liver-derived hepatitis C virus (HCV)-specific CD4(+) T cells recognize multiple HCV epitopes and produce interferon gamma. Hepatology. 32:597–603.

Bassett SE, Guerra B, Brasky K, Miskovsky E, Houghton M, Klimpel GR, Lanford RE. (2001) Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection. Hepatology. 33:1479–87.

Erickson AL, Kimura Y, Igarashi S, Eichelberger J, Houghton M, Sidney J, McKinney D, Sette A, Hughes AL, Walker CM. (2001) The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity. 15:883–95.

Merola M, Brazzoli M, Cocchiarella F, Heile JM, Helenius A, Weiner AJ, Houghton M, Abrignani S. (2001) Folding of hepatitis C virus E1 glycoprotein in a cell-free system. J. Virol. 75:11205–17.

Polakos NK, Drane D, Cox J, Ng P, Selby MJ, Chien D, O’Hagan DT, Houghton M, Paliard X. (2001) Characterization of hepatitis C virus core-specific immune responses primed in rhesus macaques by a nonclassical ISCOM vaccine. J. Immunol. 166:3589–98.

Schirren CA, Jung MC, Worzfeld T, Mamin M, Baretton G, Gerlach JT, Gruener NH, Zachoval R, Houghton M, Rau HG, Pape GR. (2001) Hepatitis C virus-specific CD4+ T cell response after liver transplantation occurs early, is multispecific, compartmentalizes to the liver, and does not correlate with recurrent disease. J. Infect. Dis. 183:1187–94.

Tseng CT, Miskovsky E, Houghton M, Klimpel GR. (2001) Characterization of liver T-cell receptor gammadelta T cells obtained from individuals chronically infected with hepatitis C virus (HCV): evidence for these T cells playing a role in the liver pathology associated with HCV infections. Hepatology. 33:1312–20.

Weiner AJ, Paliard X, Selby MJ, Medina-Selby A, Coit D, Nguyen S, Kansopon J, Arian CL, Ng P, Tucker J, Lee CT, Polakos NK, Han J, Wong S, Lu HH, Rosenberg S, Brasky KM, Chien D, Kuo G, Houghton M. (2001) Intrahepatic genetic inoculation of hepatitis C virus RNA confers cross-protective immunity. J. Virol. 75:7142–8.

Legrand E, Neau D, Galperine T, Trimoulet P, Moreau JF, Pitard V, Lacut JY, Ragnaud JM, Dupon M, Le Bail B, Bernard N, Schvoerer E, Houghton M, Fleury H, Lafon ME. (2002) CD4 T lymphocyte proliferative responses to hepatitis C virus (HCV) antigens in patients coinfected with HCV and human immunodeficiency virus who responded to anti-HCV treatment. J. Infect. Dis. 186:302–11.

Masciopinto F, Freer G, Burgio VL, Levy S, Galli-Stampino L, Bendinelli M, Houghton M, Abrignani S, Uematsu Y. (2002) Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection. Virology. 304:187–96.

Shoukry NH, Grakoui A, Houghton M, Chien DY, Ghrayeb J, Reimann KA, Walker CM. (2003) Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J. Exp. Med. 197:1645–55.

Seo MY, Abrignani S, Houghton M, Han JH. (2003) Small interfering RNA-mediated inhibition of hepatitis C virus replication in the human hepatoma cell line Huh-7. J. Virol. 77:810–2.

Masciopinto F, Giovani C, Campagnoli S, Galli-Stampino L, Colombatto P, Brunetto M, Yen TS, Houghton M, Pileri P, Abrignani S. (2004) Association of hepatitis C virus envelope proteins with exosomes. Eur. J. Immunol. 34:2834–42.

Houghton M, Abrignani S. (2004) “Vaccination against the hepatitis C viruses” in New Generation Vaccines 3rd Edition (Levine MM, Kaper JB, Rappuoli R, Liu M, Good MF. eds.) pp. 593–606. Marcel Dekker Inc., New York.

O’Hagan DT, Singh M, Dong C, Ugozzoli M, Berger K, Glazer E, Selby M, Wininger M, Ng P, Crawford K, Paliard X, Coates S, Houghton M. (2004) Cationic microparticles are a potent delivery system for a HCV DNA vaccine. Vaccine. 23:672–80.

Coates S, Choo Q-L, Kuo G, Crawford K, Dong C, Wininger M, Weiner A, Abrignani S, Houghton M. (2004) “Hepatitis C” in Vaccines: Preventing Disease & Protecting Health (De Quadros CA. ed.) pp. 150–6. Pan American Health Organisation.

Song HC, Seo MY, Stadler K, Yoo BJ, Choo QL, Coates SR, Uematsu Y, Harada T, Greer CE, Polo JM, Pileri P, Eickmann M, Rappuoli R, Abrignani S, Houghton M, Han JH. (2004) Synthesis and characterization of a native, oligomeric form of recombinant severe acute respiratory syndrome coronavirus spike glycoprotein. J. Virol. 78:10328–35.

Brazzoli M, Helenius A, Foung SK, Houghton M, Abrignani S, Merola M. (2005) Folding and dimerization of hepatitis C virus E1 and E2 glycoproteins in stably transfected CHO cells. Virology. 332:438–53.

Coates S, Choo Q-L, Kuo G, Crawford K, Dong C, Wininger M, Weiner A, Berger K, Wong S, Ralston R, Morandi M, Pileri P, Rosa D, Muchmore E, Mahoney J, Brasky K, Purcell R, Abrignani S, Houghton, M. (2005) “Protection of chimpanzees against heterologous 1a viral challenge using a gpE1/gpE2 heterodimer vaccine” in Proceedings of the 11th International Symposium on Viral Hepatitis & Liver Disease (Jilbert AR, Grgacic EVL, Vickery K, Burrell CJ, Cossart YE. eds.) pp. 118–123. Australian Center for Hepatitis Virology.

Nattermann J, Schneiders AM, Leifeld L, Langhans B, Schulz M, Inchauspe G, Matz B, Brackmann HH, Houghton M, Sauerbruch T, Spengler U. (2005) Serum antibodies against the hepatitis C virus E2 protein mediate antibody-dependent cellular cytotoxicity (ADCC). J. Hepatol. 42:499–504.

Houghton M, Abrignani S. (2005) Prospects for a vaccine against the hepatitis C virus. Nature. 436:961–6.

Rosa D, Saletti G, De Gregorio E, Zorat F, Comar C, D’Oro U, Nuti S, Houghton M, Barnaba V, Pozzato G, Abrignani S. (2005) Activation of naive B lymphocytes via CD81, a pathogenic mechanism for hepatitis C virus-associated B lymphocyte disorders. Proc. Natl. Acad. Sci. USA. 102:18544–9.

Vajdy M, Selby M, Medina-Selby A, Coit D, Hall J, Tandeske L, Chien D, Hu C, Rosa D, Singh M, Kazzaz J, Nguyen S, Coates S, Ng P, Abrignani S, Lin Y-L, Houghton M, O’Hagan D. (2006) Hepatitis C virus polyprotein vaccine formulations capable of inducing broad antibody and cellular immune responses. J. Gen. Virol. 87:2253–62.

Stamataki Z, Coates S, Evans MJ, Wininger M, Crawford K, Dong C, Fong YL, Chien D, Abrignani S, Balfe P, Rice CM, McKeating JA, Houghton M. (2007) Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies. Vaccine. 25:7773–84.

Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M. (2007) The way forward in HCV treatment – finding the right path. Nat. Rev. Drug Discov. 6:991–1000. Review. Erratum in: Nat. Rev. Drug Discov. (2008) 7:102. Nat. Rev. Drug Discov. (2008) 7:458.

Bowen DG, Shoukry NH, Grakoui A, Fuller MJ, Cawthon AG, Dong C, Hasselschwert DL, Brasky KM, Freeman GJ, Seth NP, Wucherpfennig KW, Houghton M, Walker CM. (2008) Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection. J. Virol. 82:5109–14.

Lin Y, Kwon T, Polo J, Zhu YF, Coates S, Crawford K, Dong C, Wininger M, Hall J, Selby M, Coit D, Medina-Selby A, McCoin C, Ng P, Drane D, Chien D, Han J, Vajdy M, Houghton M. (2008) Induction of broad CD4+ and CD8+ T-cell responses and cross-neutralizing antibodies against hepatitis C virus by vaccination with Th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2 and nonstructural proteins 3, 4, and 5. J. Virol. 82:7492–503.

Houghton M. (2009) Discovery of the hepatitis C virus. Liver Int. 29 Suppl 1:82–8. Review.

Houghton M. (2009) The long and winding road to the identification of the hepatitis C virus. J. Hepatol. 51:939–48.

Drane D, Maraskovsky E, Gibson R, Mitchell S, Barnden M, Moskwa A, Shaw D, Gervase B, Coates S, Houghton M, Basser R. (2009) Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX vaccine: a phase I study in healthy volunteers. Hum. Vaccin. 5:151–7.

Ray R, Meyer K, Banerjee A, Basu A, Coates S, Abrignani S, Houghton M, Frey SE, Belshe RB. (2010) Characterization of antibodies induced by vaccination with hepatitis C virus envelope glycoproteins. J. Infect. Dis. 202:862–6.

Frey SE, Houghton M, Coates S, Abrignani S, Chien D, Rosa D, Pileri P, Ray R, Di Bisceglie AM, Rinella P, Hill H, Wolff MC, Schultze V, Han JH, Scharschmidt B, Belshe RB. (2010) Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults. Vaccine. 28:6367–73.

Houghton M. (2011) Prospects for prophylactic and therapeutic vaccines against the hepatitis C viruses. Immunol. Rev. 239:99–108.

Stamataki Z, Coates S, Abrignani S, Houghton M, McKeating, J. (2011) Immunization of human volunteers with Hepatitis C virus envelope glycoproteins elicits antibodies that cross-neutralize heterologous virus strains. J. Infect. Dis. 204:811–3.

Meunier JC, Gottwein JM, Houghton M, Russell RS, Emerson SU, Bukh J, Purcell RH. (2011) Vaccine-induced cross-genotype reactive neutralizing antibodies against hepatitis C virus. J. Infect. Dis. 204:1186–90.

Houghton M. (2012) Chimp virus makes a savvy vaccine vector. Sci. Transl. Med. 4:115fs1.

Law JLM, Chen C, Wong J, Hockman D, Santer DM, Frey SE, Belshe RB, Wakita T, Bukh J, Jones CT, Rice CM, Abrignani S, Tyrrell DL, Houghton M. (2013) A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/ gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. PLoS ONE. 8:e59776. doi:10.1371/journal. pone.0059776.

Houghton M. (2013) Three isn’t the magic number. Nat. Med. 19:807.

Santer DM, Ma MM, Hockman D, Landi A, Tyrrell DL, Houghton M. (2013) Enhanced activation of memory, but not naïve, B cells in chronic hepatitis C virus-infected patients with cryoglobulinemia and advanced liver fibrosis. PLoS ONE. 8:e68308. doi: 10.1371/journal.pone.0068308.

Nourbakhsh M, Douglas DN, Pu CH, Lewis JT, Kawahara T, Lisboa LF, Wei E, Asthana S, Quiroga AD, Law LM, Chen C, Addison WR, Nelson R, Houghton M, Lehner R, Kneteman NM. (2013) Arylacetamide deacetylase: A novel host factor with important roles in the lipolysis of cellular triacylglycerol stores, VLDL assembly and HCV production. J. Hepatol. 59:336–43.

Houghton M, Law J, Tyrrell DL. (2013) An inactivated hepatitis C virus vaccine on the horizon? Gastroenterology. 145:285–8.

Grebely J, Bilodeau M, Feld JJ, Bruneau J, Fischer B, Raven JF, Roberts E, Choucha N, Myers RP, Sagan SM, Wilson JA, Bialystok F, Tyrrell DL, Houghton M, Krajden M. (2013) The Second Canadian Symposium on Hepatitis C Virus: A call to action. Can. J. Gastroenterol. 27:627–32.

Steenbergen RH, Joyce MA, Thomas BS, Jones D, Law J, Russell R, Houghton M, Tyrrell DL. (2013) Human serum leads to differentiation of human hepatoma cells, restoration of very-low-density lipoprotein secretion, and a 1000-fold increase in HCV Japanese fulminant hepatitis type 1 titers. Hepatology. 58:1907–17.

Law LMJ, Landi A, Magee WC, Tyrrell DL, Houghton M. (2013) Progress towards a hepatitis C virus vaccine. Emerg. Microbes Infect. 2:e79. doi:10.1038/emi.2013.79.

Colombatto P, Brunetto MR, Maina AM, Romagnoli V, Almasio P, Rumi MG, Ascione A, Pinzello G, Mondelli M, Muratori L, Rappuoli R, Rosa, D, Houghton M, Abrignani S, Bonino F. (2013) HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and ribavirin: a randomized controlled trial. J. Viral Hepatitis. doi: 10.1111/jvh.12163.

Houghton M. (2014) Hepatitis C: the next 25 years. Antiviral Res.110:77–8. doi: 10.1016/j.antiviral.2014.06.018.

Wong JA, Bhat R, Hockman D, Logan M, Chen C, Levin A, Frey SE, Belshe RB, Tyrrell DL, Law JL, Houghton M. (2014) Recombinant hepatitis C virus envelope glycoprotein vaccine elicits antibodies targeting multiple epitopes on the envelope glycoproteins associated with broad cross-neutralization. J Virol. 88:14278–88. doi: 10.1128/JVI.01911-14.

MacParland SA, Bilodeau M, Grebely J, Bruneau J, Cooper C, Klein M, Sagan S, Choucha N, Balfour L, Bialystok F, Krajden M, Raven J, Roberts E, Russell R, Houghton M, Tyrrell DL, Feld JJ. (2014) National CIHR Research Training Program in Hepatitis C. The 3rd Canadian Symposium on Hepatitis C Virus: expanding care in the interferon-free era. Can J Gastroenterol Hepatol. 28:481–7.

Ahmed M, Wang F, Levin A, Le C, Eltayebi Y, Houghton M, Tyrrell L, Barakat K. (2015) Targeting the Achilles heel of the hepatitis B virus: a review of current treatments against covalently closed circular DNA. Drug Discov Today. 20:548–61. doi: 10.1016/j.drudis.2015.01.008.

Logan M, Law J, Wong JA, Hockman D, Landi A, Chen C, Crawford K, Kundu J, Baldwin L, Johnson J, Dahiya A, LaChance G, Marcotrigiano J, Law M, Foung S, Tyrrell L, Houghton M.(2016) Native folding of a recombinant gpe1/gpe2 heterodimer vaccine antigen from a precursor protein fused with Fc IgG. J Virol. 91:e01552-16 doi:10.1128/JVI.01552-16.

Huang W, Wang Y, Chen C, Law JL, Houghton M, Chen L. (2016) Fabrication of flexible self-standing all-cellulose nanofibrous composite membranes for virus removal. Carbohydrate Polymers. 143:9–17. doi: 10.1016/j.carbpol.2016.02.011.

O’Shea D, Law J, Egli A, Douglas D, Lund G, Forester S, Lambert J, Law M, Burton DR, Tyrrell DL, Houghton M, Humar A, Kneteman N. (2016) Prevention of hepatitis C virus infection using a broad cross-neutralizing monoclonal antibody (AR4A) and epigallocatechin gallate. Liver Transplantation. 22:324–32. doi: 10.1002/lt.24344.

Freedman H, Logan MR, Law JL, Houghton M. (2016) Structure and Function of the Hepatitis C Virus Envelope Glycoproteins E1 and E2: Antiviral and Vaccine Targets. ACS Infect Dis. 2:749–762. Epub 2016 Aug 16

Freedman H, Logan MR, Hockman D, Leman JK,, Law JL, Houghton M. (2017) Computational Prediction of the Heterodimeric and Higher Order Structure of gpE1/gpE2 Envelope Glycoproteins Encoded by the Hepatitis C Virus (HCV). J Virol. doi: 10.1128/JVI.02309-16.

Sarhan MA, Abdel-Hakeem MS, Mason AL, Tyrrell DL, Houghton M. (2017) Glycogen Synthase Kinase 3β Inhibitors Prevent Hepatitis C Virus Release/Assembly through Perturbation of Lipid Metabolism. Scientific Reports. doi: 10.1038/ s41598-017-02648-6

Landi A, Law J, Hockman D, Logan M, Crawford K, Chen C, Kundu J, Ebensen T, Guzman CA, Deschatelets L, Krishnan L, Tyrrell DLJ, Houghton M. (2017) Superior immunogenicity of HCV envelope glycoproteins when adjuvanted with cyclic-di-AMP, a STING activator or archaeosomes. Vaccine. 35:6949– 6956 doi: 10.1016/j.vaccine.2017.10.072.

Bartenschlager R, Baumert TF, Bukh J, Houghton M, Lemon SM, Lindenbach BD, Lohmann V, Moradpour D, Pietschmann T, Rice CM, Thimme R, Wakita T. (2018). Critical challenges and emerging opportunities in Hepatitis C virus research in an era of potent antiviral therapy: Considerations for scientists and funding agencies. Virus research. 248:53–62. doi: 10.1016/j.virusres.2018.02.016

Law JLM, Logan M, Wong J, Kundu J, Hockman D, Landi A, Chen C, Crawford K, Wininger M, Johnson J, Mesa Prince C, Dudek E, Mehta N, Tyrrell DL, Houghton M. (2018) Role of the E2 Hypervariable Region (HVR1) in the Immunogenicity of a Recombinant Hepatitis C Virus Vaccine. Journal of virology. 92. pii: e02141-17. doi: 10.1128/JVI.02141-17.

Khera T, Behrendt P, Bankwitz D, Brown RJP, Todt D, Doepke M, Khan AG, Schulze K, Law J, Logan M, Hockman D, Wong JAJ, Dold L, Gonzalez-Motos V, Spengler U, Viejo-Borbolla A, Ströh LJ, Krey T, Tarr AW, Steinmann E, Manns MP, Klein F, Guzman CA, Marcotrigiano J, Houghton M, Pietschmann T. (2018) Functional and immunogenic characterization of diverse HCV glycoprotein E2 variants. J Hepatol. doi: 10.1016/j.jhep.2018.11.003

Banda DH, Perin PM, Brown RJP, Todt D, Solodenko W, Hoffmeyer P, Kumar Sahu K, Houghton M, Meuleman P, Müller R, Kirschning A, Pietschmann T.(2019) A central hydrophobic E1 region controls the pH range of hepatitis C virus membrane fusion and susceptibility to fusion inhibitors. J Hepatol. 70(6):1082–1092. doi: 10.1016/j.jhep.2019.01.033. Epub 2019 Feb 13.

Houghton M. (2019) Hepatitis C Virus: 30 Years after Its Discovery. Cold Spring Harb Perspect Med. 9(12). doi: 10.1101/cshperspect.a037069.

Akache B, Deschatelets L, Harrison BA, Dudani R, Stark FC, Jia Y, Landi A, Law JLM, Logan M, Hockman D, Kundu J, Tyrrell DL, Krishnan L, Houghton M, McCluskie MJ. (2019) Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins. Vaccines (Basel). 7(4). doi: 10.3390/vaccines7040204.

Immunoregulation

Egli A, Levin A, Santer DM, Joyce M, O’Shea D, Thomas BS, Lisboa LF, Barakat K, Bhat R, Fischer KP, Houghton M, Tyrrell DL, Kumar D, Humar A. (2014) Immunomodulatory Function of Interleukin 28B during primary infection with cytomegalovirus. J Infect Dis. 210:717–27. doi: 10.1093/infdis/jiu144.

Egli A, Santer D, Barakat K, Zand M, Levin A, Vollmer M, Weisser M, Khanna N, Kumar D, Tyrrell L, Houghton M, Battegay M, O’Shea D. (2014) Vaccine adjuvants-understanding molecular mechanisms to improve vaccines. Swiss Med Wkly. 144:w13940. doi: 10.4414/smw.2014.13940. eCollection 2014.

Egli A, Santer DM, O’Shea D, Barakat K, Syedbasha M, Vollmer M, Baluch A, Bhat R, Groenendyk J, Joyce MA, Lisboa LF, Thomas BS, Battegay M, Khanna N, Mueller T, Tyrrell DL, Houghton M, Humar A, Kumar D. (2014) IL-28B is a key regulator of B-and T-cell vaccine responses against influenza. PLoS Pathog. 10:e1004556. doi: 10.1371/journal.ppat.1004556. eCollection 2014 Dec.

Egli A, Santer DM, O’Shea D, Tyrrell DL, Houghton M. (2014) The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections. Emerging Microbes Infections. 3:e51. doi: 10.1038/emi.2014.51.

Egli A, Humar A, Widmer LA, Lisboa LF, Santer DM, Mueller T, Stelling J, Baluch A, O’Shea D, Houghton M, Kumar D. (2015) Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza Vaccination. J Infect Dis. 212:137–46. doi: 10.1093/infdis/jiv015.

Syedbasha M, Linnik J, Santer D, O’Shea D, Barakat K, Joyce M, Khanna N, Tyrrell DL, Houghton M, Egli A. (2016) An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions. J Vis Exp. doi: 10.3791/53575.

Santer DM, Minty GE, Mohamed A, Baldwin L, Bhat R, Joyce M, Egli A, Tyrrell DL, Houghton M. (2017) A novel method for detection of IFN-lambda 3 binding to cells for quantifying IFN-lambda receptor expression. J Immunol Methods. doi:10.1016/j.jim.2017.03.001.

Okoye IS, Houghton M, Tyrrell L, Barakat K, Elahi S. (2017) Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8+ T Cell Responses to Chronic Viral Infections and Cancer. Front Immunol. doi: 10.3389/fimmu.2017.01215. eCollection 2017.

Santer DM, Minty GES, Golec DP, Lu J, May J, Namdar A, Shah J, Elahi S, Proud D, Joyce M, Tyrrell DL, Houghton M. (2020) Differential expression of interferon-lambda receptor 1 splice variants determines the magnitude of the antiviral response induced by interferon-lambda 3 in human immune cells. PLoS Pathog. 16(4):e1008515. doi: 10.1371/journal.ppat.1008515

Freedman H, Kundu J, Tchesnokov EP, Law JLM, Nieman JA, Schinazi RF, Tyrrell DL, Gotte M, Houghton M. (2020) Application of Molecular Dynamics Simulations to the Design of Nucleotide Inhibitors Binding to Norovirus Polymerase. J Chem Inf Model. 60(12):6566–6578. doi: 10.1021/acs.jcim.0c00742. Epub 2020 Dec 1. PMID: 33259199; PMCID: PMC7869559.

Autoimmune Liver Disease

Landi A, Weismuller TJ, Lankisch TO, Santer DM, Tyrrell DL, Manns MP, Houghton M. (2014) Differential serum levels of eosinophilic eotaxins in primary sclerosing cholangitis, primary biliary cirrhosis, and autoimmune hepatitis. J Interferon Cytokine Res. 34(3):204–14. doi: 10.1089/jir.2013.0075.

Chronic Fatigue Syndrome

Steffen I, Tyrrell DL, Stein E, Montalvo L, Lee TH, Zhou Y, Lu K, Switzer WM, Tang S, Jia H, Hockman D, Santer DM, Logan M, Landi A, Law J, Houghton M, Simmons G. (2011) No evidence for XMRV nucleic acids, infectious virus or anti-XMRV antibodies in Canadian patients with chronic fatigue syndrome. PLoS ONE. 6:e27870.

Jason LA, Unger ER, Dimitrakoff JD, Fagin AP, Houghton M, Cook DB, Marshall GD Jr, Klimas N, Snell C. (2012) Minimum data elements for research reports on CFS. Brain Behav. Immun. 26:401–6.

Landi A, Broadhurst D, Vernon SD, Tyrrell DL, Houghton M. (2015) Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/ chronic fatigue syndrome. Cytokine. 78:27–36. doi: 10.1016/j.cyto.2015.11.018.

Gindin Y, Chung C, Jiang Z, Zhou JZ, Xu J, Billin AN, Myers RP, Goodman Z, Landi A, Houghton M, Green RM, Levy C, Kowdley KV, Bowlus CL, Muir AJ, Trauner M. (2021) A Fibrosis-Independent Hepatic Transcriptomic Signature Identifies Drivers of Disease Progression in Primary Sclerosing Cholangitis. Hepatology. 73(3):1105–1116. doi: 10.1002/hep.31488. Epub 2021 Feb 28. PMID: 32745270; PMCID: PMC8048608.

Computational Modeling

Barakat KH, Huzil JT, Jordan KE, Evangelinos C, Houghton M, Tuszynski J. (2013) A computational model for overcoming drug resistance using selective dual-inhibitors for aurora kinase A and its T217D variant. Mol. Pharm. 10:4572–89.

Barakat KH, Law J, Prunotto A, Magee WC, Evans DH, Tyrrell DL, Tuszynski J, Houghton M. (2013) Detailed computational study of the active site of the hepatitis C viral RNA polymerase to aid novel drug design. J. Chem. Inf. Model. 53:3031–43.

Anwar-Mohamed A, Barakat KH, Bhat R, Noskov SY, Tyrrell DL, Tuszynski JA,Houghton M. (2014) A human ether-á-go-go-related (hERG) ion channel atomistic model generated by long supercomputer molecular dynamics simulations and its use in predicting drug cardiotoxicity. Toxicology Letters. 230:382–92. doi: 10.1016/j.toxlet.2014.08.007.

Barakat KH, Anwar-Mohamed A, Tuszynski JA, Robins MJ, Tyrrell DL, Houghton M. (2015) A Refined Model of the HCV NS5A protein bound to daclatasvir explains drug-resistant mutations and activity against divergent genotypes. J Chem Inf Model. 55:362–73. doi: 10.1021/ci400631n.

Ahmed M, Pal A, Houghton M, Barakat K. (2016) A Comprehensive Computational Analysis for the Binding Modes of Hepatitis C Virus NS5A Inhibitors: The Question of Symmetry. ACS Infect Dis. 2:872–881.

Ahmed M, Jalily Hasani H, Ganesan A, Houghton M, Barakat K. (2017) Modeling the human Nav1.5 sodium channel: structural and mechanistic insights of ion permeation and drug blockade. Drug Des Devel Ther. doi: 10.2147/DDDT. S133944. eCollection 2017.

Barakat KH, Houghton M, Tyrrell DL, Tuszynski JA. (2017) Rational Drug Design Rational Drug Design: One Target, Many Paths to It. IGI Global. doi: 10.4018/978-1-5225-1762-7.ch044

Freedman H, Winter P, Tuszynski J, Tyrrell DL, Houghton M. (2018) A computational approach for predicting off-target toxicity of antiviral ribonucleoside analogues to mitochondrial RNA polymerase. The Journal of biological chemistry. 293:9696–9705. doi: 10.1074/jbc.RA118.002588

Ganesan A, Ahmed M, Okoye I, Arutyunova E, Babu D, Turnbull W, Kundu JK, Shields J, Agopsowicz K, Xu L, Tabana Y, Srivastava N, Zhang G, Moon T, Belovodskiy A, Hena M, Kandadai AS, Hosseini S, Hitt M, Walker J, Smylie M, West FG, Siraki AG, Lemieux MJ, Elahi S, Nieman JA, Tyrrell DL, Houghton M, Barakat K. (2019) Comprehensive in vitro characterization of PD-L1 small molecule inhibitors. Scientific Reports. 9(1):12392. doi: 10.1038/s41598-019-48826-6.

Kalyaanamoorthy S, Lamothe SM, Hou X, Moon TC, Kurata HT, Houghton M, Barakat KH. (2020) A structure-based computational workflow to predict liability and binding modes of small molecules to hERG. Sci Rep. 10(1):16262. doi: 10.1038/s41598-020-72889-5.

Freedman H, Kundu J, Tchesnokov EP, Law JLM, Nieman JA, Schinazi RF, Tyrrell DL, Gotte M, Houghton M. (2020) Application of Molecular Dynamics Simulations to the Design of Nucleotide Inhibitors Binding to Norovirus Polymerase. J Chem Inf Model.; 60(12):6566–6578. doi: 10.1021/acs.jcim.0c00742.

COVID-19

Law JLM, Logan M, Joyce MA, Landi A, Hockman D, Crawford K, Johnson J, LaChance G, Saffran HA, Shields J, Hobart E, Brassard R, Arutyunova E, Pabbaraju K, Croxen M, Tipples G, Lemieux MJ, Tyrrell DL, Houghton M. (2021) SARS-COV-2 recombinant Receptor-Binding-Domain (RBD) induces neutralizing antibodies against variant strains of SARS-CoV-2 and SARS-CoV-1. Vaccine. 39(40):5769–5779. doi: 10.1016/j.vaccine.2021.08.081. Epub 2021 Aug 26. PMID: 34481699; PMCID: PMC8387217.

Photo of Michael Houghton © University of Alberta

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