Skip to main content
SpringerLink
Log in

Virion Assembly and Release

  • Chapter
Hepatitis C Virus: From Molecular Virology to Antiviral Therapy

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 369))

Abstract

Hepatitis C Virus (HCV) particles exhibit several unusual properties that are not found in other enveloped RNA viruses, most notably their low buoyant density and interaction with serum lipoproteins. With the advent of systems to grow HCV in cell culture, the molecular basis of HCV particle assembly and release can now be addressed. The process of virus assembly involves protein–protein interactions between viral structural and nonstructural proteins and the coordinated action of host factors. This chapter reviews our current understanding of these interactions and factors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aizaki H, Morikawa K, Fukasawa M et al. (2008) Critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection. J Virol 82:5715–5724 doi: JVI.02530-07 [pii] 10.1128/JVI.02530-07

  • Albecka A, Montserret R, Krey T et al. (2011) Identification of new functional regions in hepatitis C virus envelope glycoprotein E2. J Virol 85:1777–1792 doi: JVI.02170-10 [pii] 10.1128/JVI.02170-10

  • AndrĂ© P, Komurian-Pradel F, Deforges S et al (2002) Characterization of low—and very-low-density hepatitis C virus RNA-containing particles. J Virol 76:6919–6928

    PubMed  PubMed Central  Google Scholar 

  • Appel N, Zayas M, Miller S et al (2008) Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly. PLoS Pathog 4:e1000035

    PubMed  PubMed Central  Google Scholar 

  • Ariumi Y, Kuroki M, Maki M, Ikeda M, Dansako H, Wakita T, Kato N (2011) The ESCRT system is required for hepatitis C virus production. PLoS ONE 6:e14517. doi:10.1371/journal.pone.0014517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Backes P, Quinkert D, Reiss S et al. (2010) Role of annexin A2 in the production of infectious hepatitis C virus particles. J Virol 84:5775–5789 doi: JVI.02343-09 [pii] 10.1128/JVI.02343-09

  • Barba G, Harper F, Harada T et al (1997) Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Natl Acad Sci USA 94:1200–1205

    CAS  PubMed  Google Scholar 

  • Bartenschlager R, Lohmann V, Wilkinson T, Koch JO (1995) Complex formation between the NS3 serine-type proteinase of the hepatitis C virus and NS4A and its importance for polyprotein maturation. J Virol 69:7519–7528

    CAS  PubMed  PubMed Central  Google Scholar 

  • Benga WJ, Krieger SE, Dimitrova M et al (2010) Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles. Hepatol 51:43–53. doi:10.1002/hep.23278

    Article  CAS  Google Scholar 

  • Beran RK, Lindenbach BD, Pyle AM (2009) The NS4A protein of hepatitis C virus promotes RNA-coupled ATP hydrolysis by the NS3 helicase. J Virol 83:3268–3275

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blasiole DA, Oler AT, Attie AD (2008) Regulation of ApoB secretion by the low density lipoprotein receptor requires exit from the endoplasmic reticulum and interaction with ApoE or ApoB. J Biol Chem 283:11374–11381 doi: M710457200 [pii] 10.1074/jbc.M710457200

  • Boson B, Granio O, Bartenschlager R, Cosset F-L (2011) A concerted action of hepatitis C virus P7 and nonstructural protein 2 regulates core localization at the endoplasmic reticulum and virus assembly. PLoS Pathog 7:e1002144

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boulant S, Montserret R, Hope RG et al (2006) Structural determinants that target the hepatitis C virus core protein to lipid droplets. J Biol Chem 281:22236–22247

    CAS  PubMed  Google Scholar 

  • Boulant S, Targett-Adams P, McLauchlan J (2007) Disrupting the association of hepatitis C virus core protein with lipid droplets correlates with a loss in production of infectious virus. J Gen Virol 88:2204–2213

    CAS  PubMed  Google Scholar 

  • Boulant S, Vanbelle C, Ebel C, Penin F, Lavergne JP (2005) Hepatitis C virus core protein is a dimeric alpha-helical protein exhibiting membrane protein features. J Virol 79:11353–11365

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bradley D, McCaustland K, Krawczynski K, Spelbring J, Humphrey C, Cook EH (1991) Hepatitis C virus: buoyant density of the factor VIII-derived isolate in sucrose. J Med Virol 34:206–208

    CAS  PubMed  Google Scholar 

  • Bradley DW, McCaustland KA, Cook EH, Schable CA, Ebert JW, Maynard JE (1985) Posttransfusion non-A, non-B hepatitis in chimpanzees: physicochemical evidence that the tubule-forming agent is a small, enveloped virus. Gastroenterol 88:773–779

    CAS  Google Scholar 

  • 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. Virol 332:438–453

    CAS  Google Scholar 

  • Bressanelli S, Stiasny K, Allison SL et al (2004) Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation. EMBO J 23:728–738

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cai Z, Zhang C, Chang KS et al (2005) Robust production of infectious hepatitis C virus (HCV) from stably HCV cDNA-transfected human hepatoma cells. J Virol 79:13963–13973

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chang KS, Jiang J, Cai Z, Luo G (2007) Human apolipoprotein E is required for infectivity and production of hepatitis C virus in cell culture. J Virol 81:13783–13793

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ciczora Y, Callens N, Montpellier C, Bartosch B, Cosset FL, Op de Beeck A, Dubuisson J (2005) Contribution of the charged residues of hepatitis C virus glycoprotein E2 transmembrane domain to the functions of the E1E2 heterodimer. J Gen Virol 86:2793–2798

    CAS  PubMed  Google Scholar 

  • Ciczora Y, Callens N, Penin F, Pecheur EI, Dubuisson J (2007) Transmembrane domains of hepatitis C virus envelope glycoproteins: residues involved in E1E2 heterodimerization and involvement of these domains in virus entry. J Virol 81:2372–2381

    CAS  PubMed  Google Scholar 

  • Clarke D, Griffin S, Beales L, Gelais CS, Burgess S, Harris M, Rowlands D (2006) Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro. J Biol Chem 281:37057–37068

    CAS  PubMed  Google Scholar 

  • Cocquerel L, Duvet S, Meunier JC, Pillez A, Cacan R, Wychowski C, Dubuisson J (1999) The transmembrane domain of hepatitis C virus glycoprotein E1 is a signal for static retention in the endoplasmic reticulum. J Virol 73:2641–2649

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cocquerel L, Meunier JC, Pillez A, Wychowski C, Dubuisson J (1998) A retention signal necessary and sufficient for endoplasmic reticulum localization maps to the transmembrane domain of hepatitis C virus glycoprotein E2. J Virol 72:2183–2191

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cocquerel L, Op de Beeck A, Lambot M et al (2002) Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins. EMBO J 21:2893–2902

    CAS  PubMed  PubMed Central  Google Scholar 

  • Coller KE, Heaton NS, Berger KL, Cooper JD, Saunders JL, Randall G (2012) Molecular determinants and dynamics of hepatitis C virus secretion. PLoS Pathog 8:e1002466 doi: PPATHOGENS-D-11-00707 [pii] 10.1371/journal.ppat.1002466

  • Corless L, Crump CM, Griffin SD, Harris M (2010) Vps4 and the ESCRT-III complex are required for the release of infectious hepatitis C virus particles. J Gen Virol 91:362–372 doi: vir.0.017285-0 [pii] 10.1099/vir.0.017285-0

  • Counihan NA, Rawlinson SM, Lindenbach BD (2011) Trafficking of Hepatitis C Virus Core Protein during Virus Particle Assembly. PLoS Pathog 7:e1002302 doi: PPATHOGENS-D-11-00418 [pii] 10.1371/journal.ppat.1002302

  • Cun W, Jiang J, Luo G (2010) The C-terminal alpha-helix domain of apolipoprotein E is required for interaction with nonstructural protein 5A and assembly of hepatitis C virus. J Virol 84:11532–11541 doi: JVI.01021-10 [pii] 10.1128/JVI.01021-10

  • Drummer HE, Poumbourios P (2004) Hepatitis C virus glycoprotein E2 contains a membrane-proximal heptad repeat sequence that is essential for E1E2 glycoprotein heterodimerization and viral entry. J Biol Chem 279:30066–30072

    CAS  PubMed  Google Scholar 

  • Dubuisson J, Hsu HH, Cheung RC, Greenberg HB, Russell DG, Rice CM (1994) Formation and intracellular localization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia and Sindbis viruses. J Virol 68:6147–6160

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dubuisson J, Rice CM (1996) Hepatitis C virus glycoprotein folding: disulfide bond formation and association with calnexin. J Virol 70:778–786

    CAS  PubMed  PubMed Central  Google Scholar 

  • Duvet S, Cocquerel L, Pillez A et al (1998) Hepatitis C virus glycoprotein complex localization in the endoplasmic reticulum involves a determinant for retention and not retrieval. J Biol Chem 273:32088–32095

    CAS  PubMed  Google Scholar 

  • Evans MJ, Rice CM, Goff SP (2004) Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication. Proc Natl Acad Sci U S A 101:13038–13043

    CAS  PubMed  PubMed Central  Google Scholar 

  • Failla C, Tomei L, De Francesco R (1994) Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J Virol 68:3753–3760

    CAS  PubMed  PubMed Central  Google Scholar 

  • Felmlee DJ, Sheridan DA, Bridge SH, et al. (2010) Intravascular transfer contributes to postprandial increase in numbers of very-low-density hepatitis C virus particles. Gastroenterology 139:1774-1783, 1783.e1771–1776 doi: S0016-5085(10)01142-X [pii] 10.1053/j.gastro.2010.07.047

  • Garaigorta U, Heim MH, Boyd B, Wieland S, Chisari FV (2012) Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress. J Virol 86:11043–11056 doi: JVI.07101-11 [pii] 10.1128/JVI.07101-11

  • Gastaminza P, Cheng G, Wieland S, Zhong J, Liao W, Chisari FV (2008) Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion. J Virol 82:2120–2129

    CAS  PubMed  Google Scholar 

  • Gastaminza P, Dryden KA, Boyd B, Wood MR, Law M, Yeager M, Chisari FV (2010) Ultrastructural and biophysical characterization of hepatitis C virus particles produced in cell culture. J Virol 84:10999–11009 doi: JVI.00526-10 [pii] 10.1128/JVI.00526-10

  • Gastaminza P, Kapadia SB, Chisari FV (2006) Differential biophysical properties of infectious intracellular and secreted hepatitis C virus particles. J Virol 80:11074–11081

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gouklani H, Bull RA, Beyer C et al. (2012) Hepatitis C virus nonstructural protein 5B is involved in virus morphogenesis. J Virol 86:5080–5088 doi: JVI.07089-11 [pii] 10.1128/JVI.07089-11

  • Gouttenoire J, Penin F, Moradpour D (2010) Hepatitis C virus nonstructural protein 4B: a journey into unexplored territory. Rev Med Virol 20:117–129. doi:10.1002/rmv.640

    Article  CAS  PubMed  Google Scholar 

  • Grakoui A, McCourt DW, Wychowski C, Feinstone SM, Rice CM (1993) A second hepatitis C virus-encoded proteinase. Proc Natl Acad Sci U S A 90:10583–10587

    CAS  PubMed  PubMed Central  Google Scholar 

  • Griffin SD, Beales LP, Clarke DS et al (2003) The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. FEBS Lett 535:34–38

    CAS  PubMed  Google Scholar 

  • Gusarova V, Brodsky JL, Fisher EA (2003) Apolipoprotein B100 exit from the endoplasmic reticulum (ER) is COPII-dependent, and its lipidation to very low density lipoprotein occurs post-ER. J Biol Chem 278:48051–48058 doi: M306898200 [pii] 10.1074/jbc.M306898200

  • Gusarova V, Seo J, Sullivan ML, Watkins SC, Brodsky JL, Fisher EA (2007) Golgi-associated maturation of very low density lipoproteins involves conformational changes in apolipoprotein B, but is not dependent on apolipoprotein E. J Biol Chem 282:19453–19462

    CAS  PubMed  Google Scholar 

  • He LF, Alling D, Popkin T, Shapiro M, Alter HJ, Purcell RH (1987) Determining the size of non-A, non-B hepatitis virus by filtration. J Infect Dis 156:636–640

    CAS  PubMed  Google Scholar 

  • Henne WM, Buchkovich NJ, Emr SD (2011) The ESCRT pathway. Dev Cell 21:77–91. doi:10.1016/j.devcel.2011.05.015

    Article  CAS  PubMed  Google Scholar 

  • Herker E, Harris C, Hernandez C et al. (2010) Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1. Nat Med 16:1295–1298 doi: nm.2238 [pii] 10.1038/nm.2238

  • Hijikata M, Mizushima H, Akagi T et al (1993a) Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus. J Virol 67:4665–4675

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hijikata M, Shimizu YK, Kato H et al (1993b) Equilibrium centrifugation studies of hepatitis C virus: evidence for circulating immune complexes. J Virol 67:1953–1958

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang H, Sun F, Owen DM, Li W, Chen Y, Gale M Jr, Ye J (2007) Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins. Proc Natl Acad Sci U S A 104:5848–5853

    CAS  PubMed  PubMed Central  Google Scholar 

  • Icard V, Diaz O, Scholtes C et al (2009) Secretion of hepatitis C virus envelope glycoproteins depends on assembly of apolipoprotein B positive lipoproteins. PLoS One 4:e4233. doi:10.1371/journal.pone.0004233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang J, Luo G (2009) Apolipoprotein E but not B is required for the formation of infectious hepatitis C virus particles. J Virol 83:12680–12691 doi: JVI.01476-09 [pii] 10.1128/JVI.01476-09

  • Jirasko V, Montserret R, Appel N et al (2008) Structural and functional characterization of non-structural protein 2 for its role in hepatitis C virus assembly. J Biol Chem 283:28546–28562

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jirasko V, Montserret R, Lee JY, Gouttenoire J, Moradpour D, Penin F, Bartenschlager R (2010) Structural and functional studies of nonstructural protein 2 of the hepatitis C virus reveal its key role as organizer of virion assembly. PLoS Pathog 6:e1001233. doi:10.1371/journal.ppat.1001233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones CT, Murray CL, Eastman DK, Tassello J, Rice CM (2007) Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. J Virol 81:8374–8383

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jones DM, Atoom AM, Zhang X, Kottilil S, Russell RS (2011) A genetic interaction between the core and NS3 proteins of hepatitis C virus is essential for production of infectious virus. J Virol 85:12351–12361 doi: JVI.05313-11 [pii] 10.1128/JVI.05313-11

  • Jones DM, Patel AH, Targett-Adams P, McLauchlan J (2009) The hepatitis C virus NS4B protein can trans-complement viral RNA replication and modulates production of infectious virus. J Virol 83:2163–2177 doi: JVI.01885-08 [pii] 10.1128/JVI.01885-08

  • Khromykh AA, Varnavski AN, Sedlak PL, Westaway EG (2001) Coupling between replication and packaging of flavivirus RNA: evidence derived from the use of DNA-based full-length cDNA clones of Kunjin virus. J Virol 75:4633–4640

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim S, Welsch C, Yi M, Lemon SM (2011) Regulation of the production of infectious genotype 1a hepatitis C virus by NS5A domain III. J Virol 85:6645–6656 doi: JVI.02156-10 [pii] 10.1128/JVI.02156-10

  • Klein KC, Polyak SJ, Lingappa JR (2004) Unique features of hepatitis C virus capsid formation revealed by de novo cell-free assembly. J Virol 78:9257–9269

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kolykhalov AA, Mihalik K, Feinstone SM, Rice CM (2000) Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3’ nontranslated region are essential for virus replication in vivo. J Virol 74:2046–2051

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kono Y, Hayashida K, Tanaka H, Ishibashi H, Harada M (2003) High-density lipoprotein binding rate differs greatly between genotypes 1b and 2a/2b of hepatitis C virus. J Med Virol 70:42–48

    CAS  PubMed  Google Scholar 

  • Krey T, d’Alayer J, Kikuti CM et al (2010) The disulfide bonds in glycoprotein E2 of hepatitis C virus reveal the tertiary organization of the molecule. PLoS Pathog 6:e1000762. doi:10.1371/journal.ppat.1000762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuang WF, Lin YC, Jean F et al (2004) Hepatitis C virus NS3 RNA helicase activity is modulated by the two domains of NS3 and NS4A. Biochem Biophys Res Commun 317:211–217

    CAS  PubMed  Google Scholar 

  • Kunkel M, Lorinczi M, Rijnbrand R, Lemon SM, Watowich SJ (2001) Self-assembly of nucleocapsid-like particles from recombinant hepatitis C virus core protein. J Virol 75:2119–2129

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kushima Y, Wakita T, Hijikata M (2010) A disulfide-bonded dimer of the core protein of hepatitis C virus is important for virus-like particle production. J Virol 84:9118-9127 doi: JVI.00402-10 [pii] 10.1128/JVI.00402-10

  • Lai CK, Jeng KS, Machida K, Lai MM (2010) Hepatitis C virus egress and release depend on endosomal trafficking of core protein. J Virol 84:11590–11598 doi: JVI.00587-10 [pii] 10.1128/JVI.00587-10

  • Lin C, Thomson JA, Rice CM (1995) A central region in the hepatitis C virus NS4A protein allows formation of an active NS3-NS4A serine proteinase complex in vivo and in vitro. J Virol 69:4373–4380

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lindenbach BD, Evans MJ, Syder AJ et al (2005) Complete replication of hepatitis C virus in cell culture. Science 309:623–626

    CAS  PubMed  Google Scholar 

  • Lindenbach BD, Meuleman P, Ploss A et al (2006) Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A 103:3805–3809

    CAS  PubMed  PubMed Central  Google Scholar 

  • Long G, Hiet MS, Windisch MP, Lee JY, Lohmann V, Bartenschlager R (2011) Mouse hepatic cells support assembly of infectious hepatitis C virus particles. Gastroenterology 141:1057–1066 doi: S0016-5085(11)00767-0 [pii] 10.1053/j.gastro.2011.06.010

  • Lorenz IC, Marcotrigiano J, Dentzer TG, Rice CM (2006) Structure of the catalytic domain of the hepatitis C virus NS2-3 protease. Nature 442:831–835

    CAS  PubMed  Google Scholar 

  • Luik P, Chew C, Aittoniemi J, et al. (2009) The 3-dimensional structure of a hepatitis C virus p7 ion channel by electron microscopy. Proc Natl Acad Sci U S A 106:12712–12716 doi: 0905966106 [pii] 10.1073/pnas.0905966106

  • Ma Y, Anantpadma M, Timpe JM, Shanmugam S, Singh SM, Lemon SM, Yi M (2011) Hepatitis C virus NS2 protein serves as a scaffold for virus assembly by interacting with both structural and nonstructural proteins. J Virol 85:86–97 doi: JVI.01070-10 [pii] 10.1128/JVI.01070-10

  • Ma Y, Yates J, Liang Y, Lemon SM, Yi M (2008) NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly. J Virol 82:7624–7639

    CAS  PubMed  PubMed Central  Google Scholar 

  • Majeau N, Fromentin R, Savard C, Duval M, Tremblay MJ, Leclerc D (2009) Palmitoylation of hepatitis C virus core protein is important for virion production. J Biol Chem 284:33915–33925 doi: M109.018549 [pii] 10.1074/jbc.M109.018549

  • Masaki T, Suzuki R, Murakami K et al (2008) Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles. J Virol 82:7964–7976

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumoto M, Hwang SB, Jeng KS, Zhu N, Lai MM (1996) Homotypic interaction and multimerization of hepatitis C virus core protein. Virology 218:43–51

    CAS  PubMed  Google Scholar 

  • McLauchlan J, Lemberg MK, Hope G, Martoglio B (2002) Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets. EMBO J 21:3980–3988

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meex SJ, Andreo U, Sparks JD, Fisher EA (2011) Huh-7 or HepG2 cells: which is the better model for studying human apolipoprotein-B100 assembly and secretion? J Lipid Res 52:152–158 doi: jlr.D008888 [pii] 10.1194/jlr.D008888

  • Menzel N, Fischl W, Hueging K et al. (2012) MAP-kinase regulated cytosolic phospholipase A2 activity is essential for production of infectious hepatitis C virus particles. PLoS Pathog 8:e1002829 doi: PPATHOGENS-D-12-00398 [pii] 10.1371/journal.ppat.1002829

  • Merz A, Long G, Hiet MS, et al. (2011) Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome. J Biol Chem 286:3018–3032 doi: M110.175018 [pii] 10.1074/jbc.M110.175018

  • Meunier JC, Russell RS, Engle RH, Faulk KN, Purcell RH, Emerson SU (2008) Apolipoprotein C1 association with Hepatitis C Virus. J Virol

    Google Scholar 

  • Michalak JP, Wychowski C, Choukhi A, Meunier JC, Ung S, Rice CM, Dubuisson J (1997) Characterization of truncated forms of hepatitis C virus glycoproteins. J Gen Virol 78(Pt 9):2299–2306

    CAS  PubMed  Google Scholar 

  • Miyanari Y, Atsuzawa K, Usuda N et al (2007) The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol 9:1089–1097

    CAS  PubMed  Google Scholar 

  • Modis Y, Ogata S, Clements D, Harrison SC (2004) Structure of the dengue virus envelope protein after membrane fusion. Nature 427:313–319

    CAS  PubMed  Google Scholar 

  • Montserret R, Saint N, Vanbelle C et al. (2010) NMR structure and ion channel activity of the p7 protein from hepatitis C virus. J Biol Chem 285:31446–31461 doi: M110.122895 [pii] 10.1074/jbc.M110.122895

  • Moradpour D, Englert C, Wakita T, Wands JR (1996) Characterization of cell lines allowing tightly regulated expression of hepatitis C virus core protein. Virology 222:51–63

    CAS  PubMed  Google Scholar 

  • Morikawa K, Lange CM, Gouttenoire J, Meylan E, Brass V, Penin F, Moradpour D (2011) Nonstructural protein 3–4A: the Swiss army knife of hepatitis C virus. J Viral Hepat 18:305–315. doi:10.1111/j.1365-2893.2011.01451.x

    Article  CAS  PubMed  Google Scholar 

  • Mousseau G, Kota S, Takahashi V, Frick DN, Strosberg AD (2011) Dimerization-driven interaction of hepatitis C virus core protein with NS3 helicase. J Gen Virol 92:101–111 doi: vir.0.023325-0 [pii] 10.1099/vir.0.023325-0

  • Nahmias Y, Goldwasser J, Casali M, van Poll D, Wakita T, Chung RT, Yarmush ML (2008) Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin. Hepatol 47:1437–1445

    CAS  Google Scholar 

  • Neveu G, Barouch-Bentov R, Ziv-Av A, Gerber D, Jacob Y, Einav S (2012) Identification and targeting of an interaction between a tyrosine motif within hepatitis C virus core protein and AP2M1 essential for viral assembly. PLoS Pathog 8:e1002845 doi: PPATHOGENS-D-12-00628 [pii] 10.1371/journal.ppat.1002845

  • Nielsen SU, Bassendine MF, Burt AD, Martin C, Pumeechockchai W, Toms GL (2006) Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients. J Virol 80:2418–2428

    CAS  PubMed  PubMed Central  Google Scholar 

  • Okamoto K, Moriishi K, Miyamura T, Matsuura Y (2004) Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C virus core protein. J Virol 78:6370–6380

    CAS  PubMed  PubMed Central  Google Scholar 

  • Op De Beeck A, Montserret R, Duvet S et al (2000) The transmembrane domains of hepatitis C virus envelope glycoproteins E1 and E2 play a major role in heterodimerization. J Biol Chem 275:31428–31437

    CAS  PubMed  Google Scholar 

  • Patel J, Patel AH, McLauchlan J (2001) The transmembrane domain of the hepatitis C virus E2 glycoprotein is required for correct folding of the E1 glycoprotein and native complex formation. Virology 279:58–68

    CAS  PubMed  Google Scholar 

  • Pavlovic D, Neville DC, Argaud O, Blumberg B, Dwek RA, Fischer WB, Zitzmann N (2003) The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc Natl Acad Sci U S A 100:6104–6108

    CAS  PubMed  PubMed Central  Google Scholar 

  • Phan T, Beran RK, Peters C, Lorenz IC, Lindenbach BD (2009) Hepatitis C virus NS2 protein contributes to virus particle assembly via opposing epistatic interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes. J Virol 83:8379–8395 doi: JVI.00891-09 [pii] 10.1128/JVI.00891-09

  • Phan T, Kohlway A, Dimberu P, Pyle AM, Lindenbach BD (2011) The acidic domain of hepatitis C virus NS4A contributes to RNA replication and virus particle assembly. J Virol 85:1193–1204 doi: JVI.01889-10 [pii] 10.1128/JVI.01889-10

  • Pietschmann T, Zayas M, Meuleman P et al (2009) Production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations. PLoS Pathog 5:e1000475. doi:10.1371/journal.ppat.1000475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Podevin P, Carpentier A, Pene V et al. (2010) Production of infectious hepatitis C virus in primary cultures of human adult hepatocytes. Gastroenterology doi: S0016-5085(10)01001-2 [pii] 10.1053/j.gastro.2010.06.058

  • Popescu CI, Callens N, Trinel D et al (2011) NS2 protein of hepatitis C virus interacts with structural and non-structural proteins towards virus assembly. PLoS Pathog 7:e1001278. doi:10.1371/journal.ppat.1001278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Premkumar A, Wilson L, Ewart GD, Gage PW (2004) Cation-selective ion channels formed by p7 of hepatitis C virus are blocked by hexamethylene amiloride. FEBS Lett 557:99–103

    CAS  PubMed  Google Scholar 

  • Prince AM, Huima-Byron T, Parker TS, Levine DM (1996) Visualization of hepatitis C virions and putative defective interfering particles isolated from low-density lipoproteins. J Viral Hepat 3:11–17

    CAS  PubMed  Google Scholar 

  • RouillĂ© Y, Helle F, Delgrange D et al (2006) Subcellular localization of hepatitis C virus structural proteins in a cell culture system that efficiently replicates the virus. J Virol 80:2832–2841

    PubMed  PubMed Central  Google Scholar 

  • Rustaeus S, Stillemark P, Lindberg K, Gordon D, Olofsson SO (1998) The microsomal triglyceride transfer protein catalyzes the post-translational assembly of apolipoprotein B-100 very low density lipoprotein in McA-RH7777 cells. J Biol Chem 273:5196–5203

    CAS  PubMed  Google Scholar 

  • Sakai A, Claire MS, Faulk K, Govindarajan S, Emerson SU, Purcell RH, Bukh J (2003) The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proc Natl Acad Sci U S A 100:11646–11651

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sakata N, Wu X, Dixon JL, Ginsberg HN (1993) Proteolysis and lipid-facilitated translocation are distinct but competitive processes that regulate secretion of apolipoprotein B in Hep G2 cells. J Biol Chem 268:22967–22970

    CAS  PubMed  Google Scholar 

  • Santolini E, Migliaccio G, La Monica N (1994) Biosynthesis and biochemical properties of the hepatitis C virus core protein. J Virol 68:3631–3641

    CAS  PubMed  PubMed Central  Google Scholar 

  • Scheel TK, Prentoe J, Carlsen TH, Mikkelsen LS, Gottwein JM, Bukh J (2012) Analysis of functional differences between hepatitis C virus NS5A of genotypes 1–7 in infectious cell culture systems. PLoS Pathog 8:e1002696 doi: PPATHOGENS-D-11-00309 [pii] 10.1371/journal.ppat.1002696

  • Schregel V, Jacobi S, Penin F, Tautz N (2009) Hepatitis C virus NS2 is a protease stimulated by cofactor domains in NS3. Proc Natl Acad Sci U S A 106:5342–5347

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shavinskaya A, Boulant S, Penin F, McLauchlan J, Bartenschlager R (2007) The lipid droplet binding domain of hepatitis C virus core protein is a major determinant for efficient virus assembly. J Biol Chem

    Google Scholar 

  • Siddiqi SA (2008) VLDL exits from the endoplasmic reticulum in a specialized vesicle, the VLDL transport vesicle, in rat primary hepatocytes. Biochem J 413:333–342 doi: BJ20071469 [pii] 10.1042/BJ20071469

  • Stapleford KA, Lindenbach BD (2011) Hepatitis C Virus NS2 Coordinates Virus Particle Assembly through Physical Interactions with the E1-E2 Glycoprotein and NS3-NS4A Enzyme Complexes. J Virol 85:1706–1717 doi: JVI.02268-10 [pii] 10.1128/JVI.02268-10

  • Steinmann E, Penin F, Kallis S, Patel AH, Bartenschlager R, Pietschmann T (2007) Hepatitis C Virus p7 Protein Is Crucial for Assembly and Release of Infectious Virions. PLoS Pathog 3:e103

    PubMed  PubMed Central  Google Scholar 

  • Stillemark P, BorĂ©n J, Andersson M, Larsson T, Rustaeus S, Karlsson KA, Olofsson SO (2000) The assembly and secretion of apolipoprotein B-48-containing very low density lipoproteins in McA-RH7777 cells. J Biol Chem 275:10506–10513

    CAS  PubMed  Google Scholar 

  • Tamai K, Shiina M, Tanaka N et al. (2012) Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway. Virology 422:377–385 doi: S0042-6822(11)00537-X [pii] 10.1016/j.virol.2011.11.009

  • Tedbury P, Welbourn S, Pause A, King B, Griffin S, Harris M (2011) The subcellular localization of the hepatitis C virus non-structural protein NS2 is regulated by an ion channel-independent function of the p7 protein. J Gen Virol 92:819–830 doi: vir.0.027441-0 [pii] 10.1099/vir.0.027441-0

  • Tellinghuisen TL, Foss KL, Treadaway J (2008) Regulation of hepatitis C virion production via phosphorylation of the NS5A protein. PLoS Pathog 4:e1000032

    PubMed  PubMed Central  Google Scholar 

  • Thomssen R, Bonk S, Propfe C, Heermann KH, Kochel HG, Uy A (1992) Association of hepatitis C virus in human sera with beta-lipoprotein. Med Microbiol Immunol (Berl) 181:293–300

    CAS  Google Scholar 

  • Timpe JM, Stamataki Z, Jennings A et al (2008) Hepatitis C virus cell–cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatol 47:17–24

    Google Scholar 

  • Tscherne DM, Jones CT, Evans MJ, Lindenbach BD, McKeating JA, Rice CM (2006) Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry. J Virol 80:1734–1741

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vieyres G, Thomas X, Descamps V, Duverlie G, Patel AH, Dubuisson J (2010) Characterization of the envelope glycoproteins associated with infectious hepatitis C virus. J Virol 84:10159–10168 doi: JVI.01180-10 [pii] 10.1128/JVI.01180-10

  • Wakita T, Pietschmann T, Kato T et al (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11:791–796

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Gilham D, Lehner R (2007) Proteomic and lipid characterization of apolipoprotein B-free luminal lipid droplets from mouse liver microsomes: implications for very low density lipoprotein assembly. J Biol Chem 282:33218–33226 doi: M706841200 [pii] 10.1074/jbc.M706841200

  • Welbourn S, Green R, Gamache I et al (2005) Hepatitis C virus NS2/3 processing is required for NS3 stability and viral RNA replication. J Biol Chem 280:29604–29611

    CAS  PubMed  Google Scholar 

  • Welsch S, Miller S, Romero-Brey I, et al. (2009) Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5:365–375 doi: S1931-3128(09)00098-5 [pii] 10.1016/j.chom.2009.03.007

  • Welsch S, Muller B, Krausslich HG (2007) More than one door—Budding of enveloped viruses through cellular membranes. FEBS Lett 581:2089–2097. doi:10.1016/j.febslet.2007.03.060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whidby J, Mateu G, Scarborough H, Demeler B, Grakoui A, Marcotrigiano J (2009) Blocking hepatitis C virus infection with recombinant form of envelope protein 2 ectodomain. J Virol 83:11078–11089 doi: JVI.00800-09 [pii] 10.1128/JVI.00800-09

  • Witteveldt J, Evans MJ, Bitzegeio J et al. (2009) CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells. J Gen Virol 90:48–58 doi: 90/1/48 [pii] 10.1099/vir.0.006700-0

  • Wozniak AL, Griffin S, Rowlands D, Harris M, Yi M, Lemon SM, Weinman SA (2010) Intracellular proton conductance of the hepatitis C virus p7 protein and its contribution to infectious virus production. PLoS Pathog 6:e1001087. doi:10.1371/journal.ppat.1001087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yagnik AT, Lahm A, Meola A, Roccasecca RM, Ercole BB, Nicosia A, Tramontano A (2000) A model for the hepatitis C virus envelope glycoprotein E2. Proteins 40:355–366

    CAS  PubMed  Google Scholar 

  • Yamamoto T, Takahashi S, Moriwaki Y, Hada T, Higashino K (1987) A newly discovered apolipoprotein B-containing high-density lipoprotein produced by human hepatoma cells. Biochim Biophys Acta 922:177-183 doi: 0005-2760(87)90152-4 [pii]

    Google Scholar 

  • Yao Z, Tran K, McLeod RS (1997) Intracellular degradation of newly synthesized apolipoprotein B. J Lipid Res 38:1937–1953

    Google Scholar 

  • Yasui K, Wakita T, Tsukiyama-Kohara K et al (1998) The native form and maturation process of hepatitis C virus core protein. J Virol 72:6048–6055

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ye J, Li JZ, Liu Y et al. (2009) Cideb, an ER- and lipid droplet-associated protein, mediates VLDL lipidation and maturation by interacting with apolipoprotein B. Cell Metab 9:177–190 doi: S1550-4131(08)00420-8 [pii] 10.1016/j.cmet.2008.12.013

  • Yi M, Nakamoto Y, Kaneko S, Yamashita T, Murakami S (1997) Delineation of regions important for heteromeric association of hepatitis C virus E1 and E2. Virology 231:119–129

    CAS  PubMed  Google Scholar 

  • Yi M, Villanueva RA, Thomas DL, Wakita T, Lemon SM (2006) Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in cultured human hepatoma cells. Proc Natl Acad Sci U S A 103:2310–2315

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yuasa T, Ishikawa G, Manabe S, Sekiguchi S, Takeuchi K, Miyamura T (1991) The particle size of hepatitis C virus estimated by filtration through microporous regenerated cellulose fibre. J Gen Virol 72(Pt 8):2021–2024

    CAS  PubMed  Google Scholar 

  • Zhong J, Gastaminza P, Cheng G et al (2005) Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A 102:9294–9299

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA

    Brett D. Lindenbach

Authors
  1. Brett D. Lindenbach
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brett D. Lindenbach .

Editor information

Editors and Affiliations

  1. Department for Infectious Diseases Molecular Virology, University of Heidelberg, Heidelberg, Germany

    Ralf Bartenschlager

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Lindenbach, B.D. (2013). Virion Assembly and Release. In: Bartenschlager, R. (eds) Hepatitis C Virus: From Molecular Virology to Antiviral Therapy. Current Topics in Microbiology and Immunology, vol 369. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27340-7_8

Download citation

Publish with us

Policies and ethics

Search

Navigation