Chapter 53 : Hepatitis C Virus

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Hepatitis C virus (HCV), a member of the genus in the family, is a single-stranded RNA virus that infects humans and other higher primates and has a selective tropism to the liver. Although the HCV particle itself is difficult to demonstrate, by inferring from the virions of other , the putative particle is composed of a nucleocapsid composed of the core protein and viral RNA, surrounded by a phospholipid membrane in which the viral envelope proteins are embedded. The replication cycle of the HCV can be divided into stages: binding and entry into the cell; polyprotein translation and processing; RNA replication; and packaging, assembly, and release of the virion. The current recommendations for disinfecting reusable endoscopic equipment by mechanical washing with detergent and soaking in 2% glutaraldehyde were shown to be sufficient to eliminate contamination with HCV. Hepatitis C can be transmitted vertically from mother to child. Successful eradication of hepatitis C with antiviral treatment significantly reduces, but does not eliminate completely, the risk of chronic hepatitis C (CHC). Serologic assays for detecting HCV infection were rapidly developed and improved following the initial discovery of the virus because of the urgent need to screen blood donors and prevent transmission. In general, antiviral treatment is indicated for any adult patient with CHC who is viremic and has elevated aminotransferases or histologic evidence of progressive liver disease, i.e., fibrosis extending beyond the portal tracts.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 1

Phylogenetic analysis of complete open reading frame sequences demonstrating clustering to six genotypes and subgenotypes. The major epidemiological attributes of each genotype are noted. IDUs, injection drug users. (Reprinted from reference with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 2

Geographic distribution of HCV genotypes. Genotype 1 is the most prevalent and can be seen worldwide. Genotype 3 is more common in south and Southeast Asia; genotype 4 is seen almost exclusively in patients from central Africa, Egypt, and Saudi Arabia; genotype 5 is mostly confined to South Africa; and genotype 6 is confined to Southeast Asia. (Reprinted from reference with permission of Elsevier.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 3

Electron microscopy of viral particles. (a) Immunogold electron microscopy of a viral particle from patient serum. The sample was incubated with anti-E1 polyclonal antibody and a secondary antibody conjugated to colloidal gold particles. An inner core (arrow) seems to be included within the particle. (Reprinted from reference with permission.) (b) Negative-stain electron microscopy of HCV harvested from Huh7.5 cells infected in vitro with HCV strain JFH-1. Spherical particles of uniform size with inner cores can be seen.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 4

Genome structure of HCV. (a) The positive-sense single-stranded RNA genome of HCV has one long open reading frame containing genes for three structural and seven nonstructural proteins and flanked by two UTRs. (b) Sequence and secondary structure of the 5′ UTR. The AUG start codon for the open reading frame is highlighted in stem-loop IV. (c) Sequence and secondary structure of the 3′ UTR. Arrows indicate variable base pairs in the stem of stem-loop I, and the asterisk indicates the variable nucleotide in the loop of stem-loop I.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 5

Viral replication cycle. Binding of the virus to the cell surface and internalization (a) are followed by release of the viral RNA (b), harnessing of the cellular ribosomes, and protein translation and processing (c). The viral proteins, associated with the ER membrane, promote the formation of replication complexes anchored to lipid membranous webs (d) in which the RNA-dependent polymerase NS5B creates copies of the viral RNA through a negative-strand RNA intermediate. HCV RNA is then packaged into membrane-covered viral particles (e) and exported from the cell, presumably through the exocytosis pathway (f). (Reprinted from reference with permission of Macmillan Publishers Ltd.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 6

World distribution of HCV seroprevalence. The highest prevalence is in Egypt, 22%. Other countries with a high prevalence of infection include Mongolia, Bolivia, and several sub-Saharan nations. (Reprinted from ( ) with permission.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 7

Evolution of screening methods for donated blood and the corresponding decrease in transfusion-related hepatitis. Data are shown for non-A, non-B hepatitis before the availability of anti-HCV testing and for HCV afterwards. HBsAg, hepatitis B virus surface antigen; anti-HBc, hepatitis B virus core antibodies; NAT, nucleic acid technology. (Adapted from reference .)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 8

Histopathological findings in CHC. (a) Moderate inflammatory activity. The portal area is expanded by an inflammatory infiltrate and a lymphoid follicle (black arrow). The infiltrate disrupts the limiting plate between portal area and hepatic parenchyma (“interface hepatitis,” black arrowheads). Foci of lobular inflammation can also be seen (white arrowhead) as well as an acidophil body (white arrow). Hematoxylin and eosin stain; magnification, ×400. (b) HCV-associated steatosis. The inflammatory infiltrate (arrow) is accompanied by fat droplets in hepatocytes (arrowheads). Hematoxylin and eosin stain; magnification, ×138. (Images provided by David Kleiner, National Cancer Institute, Bethesda, MD.)

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 9

Immune response to HCV infection. HCV infection induces innate and adaptive immune responses. Induction of HCV-specific cytotoxic T cells by antigen-presenting cells is crucial in viral clearance and prevention of chronic infection, through both cytopathic and noncytopathic mechanisms. Antibodies against HCV, secreted by B cells, appear late and do not seem to have an important role in viral control. Activation of nonspecific inflammatory cells causes liver injury. Chronic stimulation of lymphoid cells can induce autoimmunity and lymphoproliferative disorders, including cryoglobulinemia and lymphoma. TH, T helper; Ig, immunoglobulin; CTL, cytotoxic T lymphocyte.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 10

Clinical course and natural history of HCV infection. (a) Acute, spontaneously resolving hepatitis C. The liver enzyme elevation, symptoms, and appearance of antibodies usually lag behind viremia. Seropositivity persists for years after recovery but may decline after decades. (b) Acute infection progressing to CHC. Viral levels and enzyme elevations are relatively stable in the chronic phase. Accumulation of fibrosis occurs gradually, over many years. The gray dashed line represents the upper limit of the norm for ALT. HCVAb, anti-HCV antibodies.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Image of FIGURE 11

Evolution of treatment regimens for CHC and corresponding rates of sustained virologic response. IFN, alfa interferon; PEG-IFN, pegylated alfa interferon; RBV, ribavirin.

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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1. Agnello, V.,, G. Abel,, M. Elfahal,, G. B. Knight, and, Q. X. Zhang. 1999. Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor. Proc. Natl. Acad. Sci. USA 96: 1276612771.
2. Agolini, G.,, A. Russo, and, M. Clementi. 1999. Effect of phenolic and chlorine disinfectants on hepatitis C virus binding and infectivity. Am. J. Infect. Control 27: 236239.
3. Ali, A.,, and N. N. Zein. 2005. Hepatitis C infection: a systemic disease with extrahepatic manifestations. Clevel. Clin. J. Med. 72: 10051019.
4. Alter, H. J.,, and M. Houghton. 2000. Clinical Medical Research Award. Hepatitis C virus and eliminating post-transfusion hepatitis. Nat. Med. 6: 10821086.
5. Alter, M. J. 1997. Epidemiology of hepatitis C. Hepatology 26: 62S65S.
6. Alter, M. J. 2002. Prevention of spread of hepatitis C. Hepatology 36: S93S98.
7. Alter, M. J.,, D. Kruszon-Moran,, O. V. Nainan,, G. M. McQuillan,, F. Gao,, L. A. Moyer,, R. A. Kaslow, and, H. S. Margolis. 1999. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N. Engl. J. Med. 341: 556562.
8. Andre, P.,, G. Perlemuter,, A. Budkowska,, C. Brechot, and, V. Lotteau. 2005. Hepatitis C virus particles and lipoprotein metabolism. Semin. Liver Dis. 25: 93104.
9. Appel, N.,, T. Schaller,, F. Penin, and, R. Bartenschlager. 2006. From structure to function: new insights into hepatitis C virus RNA replication. J. Biol. Chem. 281: 98339836.
10. Armstrong, G. L.,, A. Wasley,, E. P. Simard,, G. M. McQuillan,, W. L. Kuhnert, and, M. J. Alter. 2006. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann. Intern. Med. 144: 705714.
11. Bartenschlager, R. 1999. The NS3/4A proteinase of the hepatitis C virus: unravelling structure and function of an unusual enzyme and a prime target for antiviral therapy. J. Viral Hepat. 6: 165181.
12. Barth, H.,, T. J. Liang, and, T. F. Baumert. 2006. Hepatitis C virus entry: molecular biology and clinical implications. Hepatology 44: 527535.
13. Barth, H.,, C. Schafer,, M. I. Adah,, F. Zhang,, R. J. Linhardt,, H. Toyoda,, A. Kinoshita-Toyoda,, T. Toida,, T. H. Van Kuppevelt,, E. Depla,, F. Von Weizsacker,, H. E. Blum, and, T. F. Baumert. 2003. Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J. Biol. Chem. 278: 4100341012.
14. Bartosch, B.,, J. Dubuisson, and, F. L. Cosset. 2003. Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes. J. Exp. Med. 197: 633642.
15. Berenguer, M.,, V. Aguilera,, M. Prieto,, F. San Juan,, J. M. Rayon,, S. Benlloch, and, J. Berenguer. 2006. Significant improvement in the outcome of HCV-infected transplant recipients by avoiding rapid steroid tapering and potent induction immunosuppression. J. Hepatol. 44: 717722.
16. Berg, T.,, M. von Wagner,, S. Nasser,, C. Sarrazin,, T. Heintges,, T. Gerlach,, P. Buggisch,, T. Goeser,, J. Rasenack,, G. R. Pape,, W. E. Schmidt,, B. Kallinowski,, H. Klinker,, U. Spengler,, P. Martus,, U. Alshuth, and, S. Zeuzem. 2006. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology 130: 10861097.
17. Bhola, K.,, and W. McGuire. 2007. Does avoidance of breast feeding reduce mother-to-infant transmission of hepatitis C virus infection? Arch. Dis. Child. 92: 365366.
18. Bialek, S. R.,, and N. A. Terrault. 2006. The changing epidemiology and natural history of hepatitis C virus infection. Clin. Liver Dis. 10: 697715.
19. Blackard, J. T.,, N. Kemmer, and, K. E. Sherman. 2006. Extrahepatic replication of HCV: insights into clinical manifestations and biological consequences. Hepatology 44: 1522.
20. Blight, K. J. 2007. Allelic variation in the hepatitis C virus NS4B protein dramatically influences RNA replication. J. Virol. 81: 57245736.
21. Branch, A. D.,, D. D. Stump,, J. A. Gutierrez,, F. Eng, and, J. L. Walewski. 2005. The hepatitis C virus alternate reading frame (ARF) and its family of novel products: the alternate reading frame protein/F-protein, the double-frameshift protein, and others. Semin. Liver Dis. 25: 105117.
22. Bruix, J.,, and M. Sherman. 2005. Management of hepatocellular carcinoma. Hepatology 42: 12081236.
23. Buffington, J.,, P. J. Murray,, K. Schlanger,, L. Shih,, T. Badsgard,, R. R. Hennessy,, R. Wood,, I. B. Weisfuse, and, R. A. Gunn. 2007. Low prevalence of hepatitis C virus antibody in men who have sex with men who do not inject drugs. Public Health Rep. 122 (Suppl. 2): 6367.
24. Bukh, J.,, T. Pietschmann,, V. Lohmann,, N. Krieger,, K. Faulk,, R. E. Engle,, S. Govindarajan,, M. Shapiro,, M. St Claire, and, R. Bartenschlager. 2002. Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees. Proc. Natl. Acad. Sci. USA 99: 1441614421.
25. Cacoub, P.,, C. Renou,, E. Rosenthal,, P. Cohen,, I. Loury,, V. Loustaud-Ratti,, A.-M. Yamamoto,, A.-C. Camproux,, P. Hausfater,, L. Musset,, P. Veyssier,, G. Raguin, and, J.-C. Piette for the GERMIVIC (Groupe d’Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l’Hepatite C). 2000. Extrahepatic manifestations associated with hepatitis C virus infection: a prospective multicenter study of 321 patients. Medicine (Baltimore) 79: 4756.
26. Cardoso, M. S.,, K. Koerner,, W. Hinz,, C. Lenz,, A. Schwandt, and, B. Kubanek. 1999. Hepatitis C virus stability: the issue! Vox Sang. 76: 124127.
27. Cha, T.,, E. Beall,, B. Irvine,, J. Kolberg,, D. Chien, and, M. S. Urdea. 1992. At least five related, but distinct, hepatitis C viral genotypes exist. Proc. Natl. Acad. Sci. USA 89: 71447148.
28. Chanzy, B.,, D. L. Duc-Bin,, B. Rousset,, P. Morand,, C. Morel-Baccard,, B. Marchetti,, J. Fauconnier,, M. R. Mallaret,, J. Calop,, J. P. Zarski, and, J. M. Seigneurin. 1999. Effectiveness of a manual disinfection procedure in eliminating hepatitis C virus from experimentally contaminated endoscopes. Gastrointest. Endosc. 50: 147151.
29. Charrel, R. N.,, R. de Chesse,, A. Decaudin,, P. De Micco, and, X. de Lamballerie. 2001. Evaluation of disinfectant efficacy against hepatitis C virus using a RTPCR-based method. J. Hosp. Infect. 49: 129134.
30. Chen, L.,, I. Borozan,, J. Feld,, J. Sun,, L. L. Tannis,, C. Coltescu,, J. Heathcote,, A. M. Edwards, and, I. D. McGilvray. 2005. Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology 128: 14371444.
31. Choo, Q. L.,, G. Kuo,, A. J. Weiner,, L. R. Overby,, D. W. Bradley, and, M. Houghton. 1989. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359362.
32. Chu, C. M.,, C. T. Yeh, and, Y. F. Liaw. 1999. Fulminant hepatic failure in acute hepatitis C: increased risk in chronic carriers of hepatitis B virus. Gut 45: 613617.
33. Conry-Cantilena, C.,, M. VanRaden,, J. Gibble,, J. Melpolder,, A. O. Shakil,, L. Viladomiu,, L. Cheung,, A. DiBisceglie,, J. Hoofnagle,, J. W. Shih, et al. 1996. Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. N. Engl. J. Med. 334: 16911696.
34. Cormier, E. G.,, R. J. Durso,, F. Tsamis,, L. Boussemart,, C. Manix,, W. C. Olson,, J. P. Gardner, and, T. Dragic. 2004. L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus. Proc. Natl. Acad. Sci. USA 101: 1406714072.
35. Davis, G. L.,, D. R. Nelson,, N. Terrault,, T. L. Pruett,, T. D. Schiano,, C. V. Fletcher,, C. V. Sapan,, L. N. Riser,, Y. Li,, R. J. Whitley, and, J. W. Gnann, Jr., for the Collaborative Antiviral Study Group. 2005. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transplant. 11: 941949.
36. Di Bisceglie, A. M.,, H. S. Conjeevaram,, M. W. Fried,, R. Sallie,, Y. Park,, C. Yurdaydin,, M. Swain,, D. E. Kleiner,, K. Mahaney, and, J. H. Hoofnagle. 1995. Ribavirin as therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 123: 897903.
37. Dumont, S.,, W. Cheng,, V. Serebrov,, R. K. Beran,, I. Tinoco, Jr.,, A. M. Pyle, and, C. Bustamante. 2006. RNA translocation and unwinding mechanism of HCV NS3 helicase and its coordination by ATP. Nature 439: 105108.
38. Elisofon, S. A.,, and M. M. Jonas. 2006. Hepatitis B and C in children: current treatment and future strategies. Clin. Liver Dis. 10: 133148, vii.
39. Elmowalid, G. A.,, M. Qiao,, S. H. Jeong,, B. B. Borg,, T. F. Baumert,, R. K. Sapp,, Z. Hu,, K. Murthy, and, T. J. Liang. 2007. Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees. Proc. Natl. Acad. Sci. USA 104: 84278432.
40. European Paediatric Hepatitis C Virus Network. 2005. A significant sex—but not elective cesarean section—effect on mother-to-child transmission of hepatitis C virus infection. J. Infect. Dis. 192: 18721879.
41. Evans, M. J.,, T. von Hahn,, D. M. Tscherne,, A. J. Syder,, M. Panis,, B. Wolk,, T. Hatziioannou,, J. A. McKeating,, P. D. Bieniasz, and, C. M. Rice. 2007. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446: 801805.
42. Farci, P.,, H. J. Alter,, A. Shimoda,, S. Govindarajan,, L. C. Cheung,, J. C. Melpolder,, R. A. Sacher,, J. W. Shih, and, R. H. Purcell. 1996. Hepatitis C virus-associated fulminant hepatic failure. N. Engl. J. Med. 335: 631634.
43. Fattovich, G.,, G. Giustina,, F. Degos,, F. Tremolada,, G. Diodati,, P. Almasio,, F. Nevens,, A. Solinas,, D. Mura,, J. T. Brouwer,, H. Thomas,, C. Njapoum,, C. Casarin,, P. Bonetti,, P. Fuschi,, J. Basho,, A. Tocco,, A. Bhalla,, R. Galassini,, F. Noventa,, S. W. Schalm, and, G. Realdi. 1997. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 112: 463472.
44. Feinstone, S. M.,, K. B. Mihalik,, T. Kamimura,, H. J. Alter,, W. T. London, and, R. H. Purcell. 1983. Inactivation of hepatitis B virus and non-A, non-B hepatitis by chloroform. Infect. Immun. 41: 816821.
45. Feld, J. J.,, and T. J. Liang. 2006. Hepatitis C—identifying patients with progressive liver injury. Hepatology 43: S194S206.
46. Flint, M.,, T. von Hahn,, J. Zhang,, M. Farquhar,, C. T. Jones,, P. Balfe,, C. M. Rice, and, J. A. McKeating. 2006. Diverse CD81 proteins support hepatitis C virus infection. J. Virol. 80: 1133111342.
47. Forns, X.,, and J. Bukh. 1999. The molecular biology of hepatitis C virus. Genotypes and quasispecies. Clin. Liver Dis. 3: 693716, vii.
48. Forton, D. M.,, P. Karayiannis,, N. Mahmud,, S. D. Taylor-Robinson, and, H. C. Thomas. 2004. Identification of unique hepatitis C virus quasispecies in the central nervous system and comparative analysis of internal translational efficiency of brain, liver, and serum variants. J. Virol. 78: 51705183.
49. Frank, C.,, M. K. Mohamed,, G. T. Strickland,, D. Lavanchy,, R. R. Arthur,, L. S. Magder,, T. El Khoby,, Y. Abdel-Wahab,, E. S. Aly Ohn,, W. Anwar, and, I. Sallam. 2000. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 355: 887891.
50. Fraser, C. S.,, and J. A. Doudna. 2007. Structural and mechanistic insights into hepatitis C viral translation initiation. Nat. Rev. Microbiol. 5: 2938.
51. Freeman, A. J.,, G. J. Dore,, M. G. Law,, M. Thorpe,, J. Von Overbeck,, A. R. Lloyd,, G. Marinos, and, J. M. Kaldor. 2001. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 34: 809816.
52. Friebe, P.,, and R. Bartenschlager. 2002. Genetic analysis of sequences in the 3′ nontranslated region of hepatitis C virus that are important for RNA replication. J. Virol. 76: 53265338.
53. Fried, M. W.,, M. L. Shiffman,, K. R. Reddy,, C. Smith,, G. Marinos,, F. L. Goncales, Jr.,, D. Haussinger,, M. Diago,, G. Carosi,, D. Dhumeaux,, A. Craxi,, A. Lin,, J. Hoffman, and, J. Yu. 2002. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N. Engl. J. Med. 347: 975982.
54. Gale, M.,, Jr., and E. M. Foy. 2005. Evasion of intracellular host defence by hepatitis C virus. Nature 436: 939945.
55. Galun, E.,, N. A. Terrault,, R. Eren,, A. Zauberman,, O. Nussbaum,, D. Terkieltaub,, M. Zohar,, R. Buchnik,, Z. Ackerman,, R. Safadi,, Y. Ashur,, S. Misrachi,, Y. Liberman,, L. Rivkin, and, S. Dagan. 2007. Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus: safety and antiviral activity. J. Hepatol. 46: 3744.
56. Gault, E.,, P. Soussan,, Y. Morice,, L. Sanders,, A. Berrada,, B. Rogers, and, P. Deny. 2003. Evaluation of a new serotyping assay for detection of anti-hepatitis C virus type-specific antibodies in serum samples. J. Clin. Microbiol. 41: 20842087.
57. Gish, R. G.,, S. Arora,, K. Rajender Reddy,, D. R. Nelson,, C. O’Brien,, Y. Xu, and, B. Murphy. 2007. Virological response and safety outcomes in therapy-naïve patients treated for chronic hepatitis C with taribavirin or ribavirin in combination with pegylated interferon alfa-2a: a randomized, phase 2 study. J. Hepatol. 47: 5159.
58. Glynn, S. A.,, D. J. Wright,, S. H. Kleinman,, D. Hirschkorn,, Y. Tu,, C. Heldebrant,, R. Smith,, C. Giachetti,, J. Gallarda, and, M. P. Busch. 2005. Dynamics of viremia in early hepatitis C virus infection. Transfusion (Paris) 45: 9941002.
59. Golden-Mason, L.,, and H. R. Rosen. 2006. Natural killer cells: primary target for hepatitis C virus immune evasion strategies? Liver Transplant. 12: 363372.
60. Gosert, R.,, D. Egger,, V. Lohmann,, R. Bartenschlager,, H. E. Blum,, K. Bienz, and, D. Moradpour. 2003. Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J. Virol. 77: 54875492.
61. Grakoui, A.,, N. H. Shoukry,, D. J. Woollard,, J. H. Han,, H. L. Hanson,, J. Ghrayeb,, K. K. Murthy,, C. M. Rice, and, C. M. Walker. 2003. HCV persistence and immune evasion in the absence of memory T cell help. Science 302: 659662.
62. Grebely, J.,, B. Conway,, J. D. Raffa,, C. Lai,, M. Krajden, and, M. W. Tyndall. 2006. Hepatitis C virus reinfection in injection drug users. Hepatology 44: 11391145.
63. Griffin, S.,, D. Clarke,, C. McCormick,, D. Rowlands, and, M. Harris. 2005. Signal peptide cleavage and internal targeting signals direct the hepatitis C virus p7 protein to distinct intracellular membranes. J. Virol. 79: 1552515536.
64. Guido, M.,, F. Bortolotti,, G. Leandro,, P. Jara,, L. Hierro,, J. Larrauri,, C. Barbera,, R. Giacchino,, L. Zancan,, F. Balli,, C. Crivellaro,, E. Cristina,, A. Pucci, and, M. Rugge. 2003. Fibrosis in chronic hepatitis C acquired in infancy: is it only a matter of time? Am. J. Gastroenterol. 98: 660663.
65. Hadziyannis, S. J.,, H. Sette, Jr.,, T. R. Morgan,, V. Balan,, M. Diago,, P. Marcellin,, G. Ramadori,, H. Bodenheimer, Jr.,, D. Bernstein,, M. Rizzetto,, S. Zeuzem,, P. J. Pockros,, A. Lin, and, A. M. Ackrill. 2004. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann. Intern. Med. 140: 346355.
66. Hauri, A. M.,, G. L. Armstrong, and, Y. J. Hutin. 2004. The global burden of disease attributable to contaminated injections given in health care settings. Int. J. STD AIDS 15: 716.
67. Heller, T.,, and B. Rehermann. 2005. Acute hepatitis C: a multifaceted disease. Semin. Liver Dis. 25: 717.
68. Heller, T.,, S. Saito,, J. Auerbach,, T. Williams,, T. R. Moreen,, A. Jazwinski,, B. Cruz,, N. Jeurkar,, R. Sapp,, G. Luo, and, T. J. Liang. 2005. An in vitro model of hepatitis C virion production. Proc. Natl. Acad. Sci. USA 102: 25792583.
69. Heo, T. H.,, S. M. Lee,, B. Bartosch,, F. L. Cosset, and, C. Y. Kang. 2006. Hepatitis C virus E2 links soluble human CD81 and SR-B1 protein. Virus Res. 121: 5864.
70. Hezode, C.,, F. Roudot-Thoraval,, E. S. Zafrani,, D. Dhumeaux, and, J. M. Pawlotsky. 2004. Different mechanisms of steatosis in hepatitis C virus genotypes 1 and 3 infections. J. Viral Hepat. 11: 455458.
71. Hofmann, W. P.,, S. Zeuzem, and, C. Sarrazin. 2005. Hepatitis C virus-related resistance mechanisms to interferon alpha-based antiviral therapy. J. Clin. Virol. 32: 8691.
72. Hoofnagle, J. H. 2002. Course and outcome of hepatitis C. Hepatology 36: S21S29.
73. Hoofnagle, J. H.,, K. D. Mullen,, D. B. Jones,, V. Rustgi,, A. Di Bisceglie,, M. Peters,, J. G. Waggoner,, Y. Park, and, E. A. Jones. 1986. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N. Engl. J. Med. 315: 15751578.
74. Hoofnagle, J. H.,, and L. B. Seeff. 2006. Peginterferon and ribavirin for chronic hepatitis C. N. Engl. J. Med. 355: 24442451.
75. Houghton, M.,, and S. Abrignani. 2005. Prospects for a vaccine against the hepatitis C virus. Nature 436: 961966.
76. Hu, K. Q.,, and M. J. Tong. 1999. The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States. Hepatology 29: 13111316.
77. Huang, Y.,, K. Staschke,, R. De Francesco, and, S. L. Tan. 2007. Phosphorylation of hepatitis C virus NS5A non-structural protein: a new paradigm for phosphorylation-dependent viral RNA replication? Virology 364: 19.
78. Iacobellis, A.,, M. Siciliano,, F. Perri,, B. E. Annicchiarico,, G. Leandro,, N. Caruso,, L. Accadia,, G. Bombardieri, and, A. Andriulli. 2007. Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study. J. Hepatol. 46: 206212.
79. Ilan, E.,, J. Arazi,, O. Nussbaum,, A. Zauberman,, R. Eren,, I. Lubin,, L. Neville,, O. Ben-Moshe,, A. Kischitzky,, A. Litchi,, I. Margalit,, J. Gopher,, S. Mounir,, W. Cai,, N. Daudi,, A. Eid,, O. Jurim,, A. Czerniak,, E. Galun, and, S. Dagan. 2002. The hepatitis C virus (HCV)-Trimera mouse: a model for evaluation of agents against HCV. J. Infect. Dis. 185: 153161.
80. Jagger, J.,, V. Puro, and, G. De Carli. 2002. Occupational transmission of hepatitis C virus. JAMA 288: 1469.
81. Jones, C. T.,, C. L. Murray,, D. K. Eastman,, J. Tassello, and, C. M. Rice. 2007. Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. J. Virol. 81: 83748383.
82. Jopling, C. L.,, M. Yi,, A. M. Lancaster,, S. M. Lemon, and, P. Sarnow. 2005. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309: 15771581.
83. Kaito, M.,, S. Watanabe,, K. Tsukiyama-Kohara,, K. Yamaguchi,, Y. Kobayashi,, M. Konishi,, M. Yokoi,, S. Ishida,, S. Suzuki, and, M. Kohara. 1994. Hepatitis C virus particle detected by immunoelectron microscopic study. J. Gen. Virol. 75 (Pt. 7) : 17551760.
84. Kamal, S. M.,, A. Amin,, M. Madwar,, C. S. Graham,, Q. He,, A. Al Tawil,, J. Rasenack,, T. Nakano,, B. Robertson,, A. Ismail, and, M. J. Koziel. 2004. Cellular immune responses in seronegative sexual contacts of acute hepatitis C patients. J. Virol. 78: 1225212258.
85. Kamal, S. M.,, A. E. Fouly,, R. R. Kamel,, B. Hockenjos,, A. Al Tawil,, K. E. Khalifa,, Q. He,, M. J. Koziel,, K. M. El Naggar,, J. Rasenack, and, N. H. Afdhal. 2006. Peginterferon alfa-2b therapy in acute hepatitis C: impact of onset of therapy on sustained virologic response. Gastroenterology 130: 632638.
86. Kamal, S. M.,, K. N. Moustafa,, J. Chen,, J. Fehr,, A. Abdel Moneim,, K. E. Khalifa,, L. A. El Gohary,, A. H. Ramy,, M. A. Madwar,, J. Rasenack, and, N. H. Afdhal. 2006. Duration of peginterferon therapy in acute hepatitis C: a randomized trial. Hepatology 43: 923931.
87. Kato, T.,, T. Matsumura,, T. Heller,, S. Saito,, R. K. Sapp,, K. Murthy,, T. Wakita, and, T. J. Liang. 2007. Production of infectious hepatitis C virus of various genotypes in cell cultures. J. Virol. 81: 44054411.
88. Kenny-Walsh, E., for The Irish Hepatology Research Group. 1999. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. N. Engl. J. Med. 340: 12281233.
89. Khakoo, S. I.,, C. L. Thio,, M. P. Martin,, C. R. Brooks,, X. Gao,, J. Astemborski,, J. Cheng,, J. J. Goedert,, D. Vlahov,, M. Hilgartner,, S. Cox,, A. M. Little,, G. J. Alexander,, M. E. Cramp,, S. J. O’Brien,, W. M. Rosenberg,, D. L. Thomas, and, M. Carrington. 2004. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 305: 872874.
90. Kleiner, D. E. 2005. The liver biopsy in chronic hepatitis C: a view from the other side of the microscope. Semin. Liver Dis. 25: 5264.
91. Kuo, G.,, Q. L. Choo,, H. J. Alter,, G. L. Gitnick,, A. G. Redeker,, R. H. Purcell,, T. Miyamura,, J. L. Dienstag,, M. J. Alter,, C. E. Stevens, et al. 1989. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244: 362364.
92. Kweon, S. S.,, M. H. Shin,, H. J. Song,, D. Y. Jeon, and, J. S. Choi. 2006. Seroprevalence and risk factors for hepatitis C virus infection among female commercial sex workers in South Korea who are not intravenous drug users. Am. J. Trop. Med. Hyg. 74: 11171121.
93. Lanford, R. E.,, C. Bigger,, S. Bassett, and, G. Klimpel. 2001. The chimpanzee model of hepatitis C virus infections. ILAR J. 42: 117126.
94. Lázaro, C. A.,, M. Chang,, W. Tang,, J. Campbell,, D. G. Sullivan,, D. R. Gretch,, L. Corey,, R. W. Coombs, and, N. Fausto. 2007. Hepatitis C virus replication in transfected and serum-infected cultured human fetal hepatocytes. Am. J. Pathol. 170: 478489.
95. Li, K.,, E. Foy,, J. C. Ferreon,, M. Nakamura,, A. C. Ferreon,, M. Ikeda,, S. C. Ray,, M. Gale, Jr., and, S. M. Lemon. 2005. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc. Natl. Acad. Sci. USA 102: 29922997.
96. Liang, T. J. 2007. Shortened therapy for hepatitis C virus genotype 2 or 3—is less more? N. Engl. J. Med. 357: 176178.
97. Lindahl, K.,, L. Stahle,, A. Bruchfeld, and, R. Schvarcz. 2005. High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology 41: 275279.
98. Lohmann, V.,, F. Korner,, J. Koch,, U. Herian,, L. Theilmann, and, R. Bartenschlager. 1999. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285: 110113.
99. Lutchman, G.,, S. Danehower,, B. C. Song,, T. J. Liang,, J. H. Hoofnagle,, M. Thomson, and, M. G. Ghany. 2007. Mutation rate of the hepatitis C virus NS5B in patients undergoing treatment with ribavirin monotherapy. Gastroenterology 132: 17571766.
100. Major, M. E.,, H. Dahari,, K. Mihalik,, M. Puig,, C. M. Rice,, A. U. Neumann, and, S. M. Feinstone. 2004. Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees. Hepatology 39: 17091720.
101. Makuwa, M.,, S. Souquiere,, P. Telfer,, E. Leroy,, O. Bourry,, P. Rouquet,, S. Clifford,, E. J. Wickings,, P. Roques, and, F. Simon. 2003. Occurrence of hepatitis viruses in wild-born nonhuman primates: a 3 year (1998–2001) epidemiological survey in Gabon. J. Med. Primatol. 32: 307314.
102. Manns, M. P.,, J. G. McHutchison,, S. C. Gordon,, V. K. Rustgi,, M. Shiffman,, R. Reindollar,, Z. D. Goodman,, K. Koury,, M. Ling, and, J. K. Albrecht. 2001. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358: 958965.
103. Martell, M.,, J. I. Esteban,, J. Quer,, J. Genesca,, A. Weiner,, R. Esteban,, J. Guardia, and, J. Gomez. 1992. Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J. Virol. 66: 32253229.
104. Mast, E. E.,, L. Y. Hwang,, D. S. Seto,, F. S. Nolte,, O. V. Nainan,, H. Wurtzel, and, M. J. Alter. 2005. Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J. Infect. Dis. 192: 18801889.
105. McHutchison, J. G.,, M. Manns,, K. Patel,, T. Poynard,, K. L. Lindsay,, C. Trepo,, J. Dienstag,, W. M. Lee,, C. Mak,, J. J. Garaud, and, J. K. Albrecht. 2002. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 123: 10611069.
106. McIntyre, P. G.,, K. Tosh, and, W. McGuire. 2006. Caesaren section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission. Cochrane Database of Systematic Reviews, issue 4.
107. Meola, A.,, A. Sbardellati,, B. Bruni Ercole,, M. Cerretani,, M. Pezzanera,, A. Ceccacci,, A. Vitelli,, S. Levy,, A. Nicosia,, C. Traboni,, J. McKeating, and, E. Scarselli. 2000. Binding of hepatitis C virus E2 glycoprotein to CD81 does not correlate with species permissiveness to infection. J. Virol. 74: 59335938.
108. Mercer, D. F.,, D. E. Schiller,, J. F. Elliott,, D. N. Douglas,, C. Hao,, A. Rinfret,, W. R. Addison,, K. P. Fischer,, T. A. Churchill,, J. R. Lakey,, D. L. Tyrrell, and, N. M. Kneteman. 2001. Hepatitis C virus replication in mice with chimeric human livers. Nat. Med. 7: 927933.
109. Meyers, C. M.,, L. B. Seeff,, C. O. Stehman-Breen, and, J. H. Hoofnagle. 2003. Hepatitis C and renal disease: an update. Am. J. Kidney Dis. 42: 631657.
110. Meylan, E.,, J. Curran,, K. Hofmann,, D. Moradpour,, M. Binder,, R. Bartenschlager, and, J. Tschopp. 2005. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437: 11671172.
111. Modi, A. A.,, and J. J. Feld. 2007. Viral hepatitis and HIV in Africa. AIDS Rev. 9: 2539.
112. Moradpour, D.,, F. Penin, and, C. M. Rice. 2007. Replication of hepatitis C virus. Nat. Rev. Microbiol. 5: 453463.
113. Moriya, K.,, H. Fujie,, Y. Shintani,, H. Yotsuyanagi,, T. Tsutsumi,, K. Ishibashi,, Y. Matsuura,, S. Kimura,, T. Miyamura, and, K. Koike. 1998. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat. Med. 4: 10651067.
114. Neumann, A. U.,, N. P. Lam,, H. Dahari,, D. R. Gretch,, T. E. Wiley,, T. J. Layden, and, A. S. Perelson. 1998. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282: 103107.
115. Nevens, F.,, T. Roskams,, H. Van Vlierberghe,, Y. Horsmans,, D. Sprengers,, A. Elewaut,, V. Desmet,, G. Leroux-Roels,, E. Quinaux,, E. Depla,, S. Dincq,, C. Vander Stichele,, G. Maertens, and, F. Hulstaert. 2003. A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C. Hepatology 38: 12891296.
116. Nguyen, M. H.,, and E. B. Keeffe. 2005. Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6. Clin. Gastroenterol. Hepatol. 3: S97S101.
117. Ostapowicz, G.,, R. J. Fontana,, F. V. Schiødt,, A. Larson,, T. J. Davern,, S. H. B. Han,, T. M. McCashland,, A. O. Shakil,, J. E. Hay,, L. Hynan,, J. S. Crippin,, A. T. Blei,, G. Samuel,, J. Reisch,, W. M. Lee, and the U.S. Acute Liver Failure Study Group. 2002. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann. Intern. Med. 137: 947954.
118. Pawlotsky, J. M. 2003. Hepatitis C virus genetic variability: pathogenic and clinical implications. Clin. Liver Dis. 7: 4566.
119. Pawlotsky, J. M. 2002. Use and interpretation of virological tests for hepatitis C. Hepatology 36: S65S73.
120. Pawlotsky, J. M.,, S. Chevaliez, and, J. G. McHutchison. 2007. The hepatitis C virus life cycle as a target for new antiviral therapies. Gastroenterology 132: 19791998.
121. Peffault de Latour, R.,, V. Levy,, T. Asselah,, P. Marcellin,, C. Scieux,, L. Ades,, R. Traineau,, A. Devergie,, P. Ribaud,, H. Esperou,, E. Gluckman,, D. Valla, and, G. Socie. 2004. Long-term outcome of hepatitis C infection after bone marrow transplantation. Blood 103: 16181624.
122. Perez, R. M.,, A. S. Ferreira,, J. O. Medina-Pestana,, M. Cendoroglo-Neto,, V. P. Lanzoni,, A. E. Silva, and, M. L. Ferraz. 2006. Is hepatitis C more aggressive in renal transplant patients than in patients with end-stage renal disease? J. Clin. Gastroenterol. 40: 444448.
123. Perz, J. F.,, L. A. Farrington,, C. Pecoraro,, Y. J. Hutin, and, G. L. Armstrong. 2004. Estimated global prevalence of hepatitis C virus infection. Annual meeting of the Infectious Diseases Society of America, Boston, MA.
124. Pietschmann, T.,, and R. Bartenschlager. 2003. Tissue culture and animal models for hepatitis C virus. Clin. Liver Dis. 7: 2343.
125. Pileri, P.,, Y. Uematsu,, S. Campagnoli,, G. Galli,, F. Falugi,, R. Petracca,, A. J. Weiner,, M. Houghton,, D. Rosa,, G. Grandi, and, S. Abrignani. 1998. Binding of hepatitis C virus to CD81. Science 282: 938941.
126. Polis, C. B.,, S. N. Shah,, K. E. Johnson, and, A. Gupta. 2007. Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: a meta-analysis. Clin. Infect. Dis. 44: 11231131.
127. Poynard, T.,, P. Bedossa, and, P. Opolon for the OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC Groups. 1997. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 349: 825832.
128. Poynard, T.,, P. Cacoub,, V. Ratziu,, R. P. Myers,, M. H. Dezailles,, A. Mercadier,, P. Ghillani,, F. Charlotte,, J. C. Piette, and, J. Moussalli. 2002. Fatigue in patients with chronic hepatitis C. J. Viral Hepat. 9: 295303.
129. Poynard, T.,, V. Ratziu,, J. McHutchison,, M. Manns,, Z. Goodman,, S. Zeuzem,, Z. Younossi, and, J. Albrecht. 2003. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 38: 7585.
130. Rehermann, B. 2007. Chronic infections with hepato-tropic viruses: mechanisms of impairment of cellular immune responses. Semin. Liver Dis. 27: 152160.
131. Rehermann, B.,, and M. Nascimbeni. 2005. Immunology of hepatitis B virus and hepatitis C virus infection. Nat. Rev. Immunol. 5: 215229.
132. Rockstroh, J. K.,, and U. Spengler. 2004. HIV and hepatitis C virus coinfection. Lancet Infect. Dis. 4: 437444.
133. Romero, A. I.,, M. Lagging,, J. Westin,, A. P. Dhillon,, L. B. Dustin,, J. M. Pawlotsky,, A. U. Neumann,, C. Ferrari,, G. Missale,, B. L. Haagmans,, S. W. Schalm,, S. Zeuzem,, F. Negro,, E. Verheij-Hart, and, K. Hellstrand. 2006. Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection. J. Infect. Dis. 194: 895903.
134. Roque-Afonso, A. M.,, D. Ducoulombier,, G. Di Liberto,, R. Kara,, M. Gigou,, E. Dussaix,, D. Samuel, and, C. Feray. 2005. Compartmentalization of hepatitis C virus genotypes between plasma and peripheral blood mononuclear cells. J. Virol. 79: 63496357.
135. Rotman, Y.,, and R. Tur-Kaspa. 2001. Transmission of hepatitis B and C viruses—update. Isr. Med. Assoc. J. 3: 357359.
136. Sattar, S. A.,, J. Tetro,, V. S. Springthorpe, and, A. Giulivi. 2001. Preventing the spread of hepatitis B and C viruses: where are germicides relevant? Am. J. Infect. Control 29: 187197.
137. Scarselli, E.,, H. Ansuini,, R. Cerino,, R. M. Roccasecca,, S. Acali,, G. Filocamo,, C. Traboni,, A. Nicosia,, R. Cortese, and, A. Vitelli. 2002. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J. 21: 50175025.
138. Schiano, T. D.,, M. Charlton,, Z. Younossi,, E. Galun,, T. Pruett,, R. Tur-Kaspa,, R. Eren,, S. Dagan,, N. Graham,, P. V. Williams, and, J. Andrews. 2006. Monoclonal antibody HCV-AbXTL68 in patients undergoing liver transplantation for HCV: results of a phase 2 randomized study. Liver Transplant. 12: 13811389.
139. Scott, J. D.,, and D. R. Gretch. 2007. Molecular diagnostics of hepatitis C virus infection: a systematic review. JAMA 297: 724732.
140. Seme, K.,, M. Poljak,, D. Z. Babic,, T. Mocilnik, and, A. Vince. 2005. The role of core antigen detection in management of hepatitis C: a critical review. J. Clin. Virol. 32: 92101.
141. Shepard, C. W.,, L. Finelli, and, M. J. Alter. 2005. Global epidemiology of hepatitis C virus infection. Lancet Infect. Dis. 5: 558567.
142. Shiffman, M. L.,, F. Suter,, B. R. Bacon,, D. Nelson,, H. Harley,, R. Sola,, S. D. Shafran,, K. Barange,, A. Lin,, A. Soman, and, S. Zeuzem. 2007. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N. Engl. J. Med. 357: 124134.
143. Shire, N. J.,, J. A. Welge, and, K. E. Sherman. 2007. Response rates to pegylated interferon and ribavirin in HCV/HIV coinfection: a research synthesis. J. Viral Hepat. 14: 239248.
144. Shoukry, N. H.,, A. Grakoui,, M. Houghton,, D. Y. Chien,, J. Ghrayeb,, K. A. Reimann, and, C. M. Walker. 2003. Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J. Exp. Med. 197: 16451655.
145. Simmonds, P.,, J. Bukh,, C. Combet,, G. Deleage,, N. Enomoto,, S. Feinstone,, P. Halfon,, G. Inchauspe,, C. Kuiken,, G. Maertens,, M. Mizokami,, D. G. Murphy,, H. Okamoto,, J. M. Pawlotsky,, F. Penin,, E. Sablon,, I. T. Shin,, L. J. Stuyver,, H. J. Thiel,, S. Viazov,, A. J. Weiner, and, A. Widell. 2005. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 42: 962973.
146. Sjogren, M. H.,, R. Sjogren, Jr.,, M. F. Lyons,, M. Ryan,, J. Santoro,, C. Smith,, K. R. Reddy,, H. Bonkovsky,, B. Huntley, and, S. Faris-Young. 2007. Antiviral response of HCV genotype 1 to consensus interferon and ribavirin versus pegylated interferon and ribavirin. Dig. Dis. Sci. 52: 15401547.
147. Soza, A.,, J. E. Everhart,, M. G. Ghany,, E. Doo,, T. Heller,, K. Promrat,, Y. Park,, T. J. Liang, and, J. H. Hoofnagle. 2002. Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C. Hepatology 36: 12731279.
148. Strasser, S. I.,, D. Myerson,, C. L. Spurgeon,, K. M. Sullivan,, B. Storer,, H. G. Schoch,, S. Kim,, M. E. Flowers, and, G. B. McDonald. 1999. Hepatitis C virus infection and bone marrow transplantation: a cohort study with 10-year follow-up. Hepatology 29: 18931899.
149. Sulkowski, M. S.,, and Y. Benhamou. 2007. Therapeutic issues in HIV/HCV-coinfected patients. J. Viral Hepat. 14: 371386.
150. Tahan, V.,, C. Karaca,, B. Yildirim,, A. Bozbas,, R. Ozaras,, K. Demir,, E. Avsar,, A. Mert,, F. Besisik,, S. Kaymakoglu,, H. Senturk,, Y. Cakaloglu,, C. Kalayci,, A. Okten, and, N. Tozun. 2005. Sexual transmission of HCV between spouses. Am. J. Gastroenterol. 100: 821824.
151. Terrault, N. A. 2002. Sexual activity as a risk factor for hepatitis C. Hepatology 36: S99S105.
152. Thuluvath, P. J.,, K. L. Krok,, D. L. Segev, and, H. Y. Yoo. 2007. Trends in post-liver transplant survival in patients with hepatitis C between 1991 and 2001 in the United States. Liver Transplant. 13: 719724.
153. Vandelli, C.,, F. Renzo,, L. Romano,, S. Tisminetzky,, M. De Palma,, T. Stroffolini,, E. Ventura, and, A. Zanetti. 2004. Lack of evidence of sexual transmission of hepatitis C among monogamous couples: results of a 10-year prospective follow-up study. Am. J. Gastroenterol. 99: 855859.
154. Vento, S.,, T. Garofano,, C. Renzini,, F. Cainelli,, F. Casali,, G. Ghironzi,, T. Ferraro, and, E. Concia. 1998. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N. Engl. J. Med. 338: 286290.
155. Voisset, C.,, and J. Dubuisson. 2004. Functional hepatitis C virus envelope glycoproteins. Biol. Cell 96: 413420.
156. von Hahn, T.,, J. C. Yoon,, H. Alter,, C. M. Rice,, B. Rehermann,, P. Balfe, and, J. A. McKeating. 2007. Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology 132: 667678.
157. Wakita, T.,, T. Pietschmann,, T. Kato,, T. Date,, M. Miyamoto,, Z. Zhao,, K. Murthy,, A. Habermann,, H. G. Krausslich,, M. Mizokami,, R. Bartenschlager, and, T. J. Liang. 2005. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med. 11: 791796.
158. Weinbaum, C. M.,, K. M. Sabin, and, S. S. Santibanez. 2005. Hepatitis B, hepatitis C, and HIV in correctional populations: a review of epidemiology and prevention. AIDS 19 (Suppl. 3) : S41S46.
159. Welbourn, S.,, and A. Pause. 2007. The hepatitis C virus NS2/3 protease. Curr. Issues Mol. Biol. 9: 6369.
160. Wells, J. T.,, M. R. Lucey, and, A. Said. 2006. Hepatitis C in transplant recipients of solid organs, other than liver. Clin. Liver Dis. 10: 901917.
161. World Health Organization. 2007. International Travel and Health. World Health Organization, Geneva, Switzerland.
162. Wu, J. Z. 2001. Internally located signal peptides direct hepatitis C virus polyprotein processing in the ER membrane. IUBMB Life 51: 1923.
163. Xie, Z. C.,, J. I. Riezu-Boj,, J. J. Lasarte,, J. Guillen,, J. H. Su,, M. P. Civeira, and, J. Prieto. 1998. Transmission of hepatitis C virus infection to tree shrews. Virology 244: 513520.
164. Yazdanpanah, Y.,, G. De Carli,, B. Migueres,, F. Lot,, M. Campins,, C. Colombo,, T. Thomas,, S. Deuffic-Burban,, M. H. Prevot,, M. Domart,, A. Tarantola,, D. Abiteboul,, P. Deny,, S. Pol,, J. C. Desenclos,, V. Puro, and, E. Bouvet. 2005. Risk factors for hepatitis C virus transmission to health care workers after occupational exposure: a European case-control study. Clin. Infect. Dis. 41: 14231430.
165. Yi, M.,, and S. M. Lemon. 2003. 3′ nontranslated RNA signals required for replication of hepatitis C virus RNA. J. Virol. 77: 35573568.
166. Yi, M.,, R. A. Villanueva,, D. L. Thomas,, T. Wakita, and, S. M. Lemon. 2006. Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in cultured human hepatoma cells. Proc. Natl. Acad. Sci. USA 103: 23102315.


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Viral proteins and their function in the viral life cycle

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Tissue culture model systems

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
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Treatment of CHC

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53
Generic image for table

Specifically targeted antiviral therapeutic agents against hepatitis C in clinical trials

Citation: Rotman Y, Liang T. 2009. Hepatitis C Virus, p 1215-1240. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch53

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