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Functional Characterization of Apolipoproteins in the HCV Life Cycle

  • Luhua Qiao
  • Guangxiang (George) LuoEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1911)

Abstract

Apolipoprotein E (apoE) plays dual functions in the HCV life cycle by promoting HCV infection and virion assembly and production. ApoE is a structural component on the HCV envelope. It mediates HCV cell attachment through specific interactions with the cell surface receptors such as syndecan-1 (SDC-1) and SDC-2 heparan sulfate proteoglycans (HSPGs). It also interacts with NS5A and E2, resulting in an enhancement of HCV morphogenesis. It can bind HCV extracellularly and promotes HCV infection. It is critical for HCV cell-to-cell transmission and may also play a role in HCV persistence by interfering with the action of HCV-neutralizing antibodies. Other apolipoproteins particularly apoB and apoC1 were also found on the HCV envelope, but their roles in the HCV life cycle remain unclear. In the last decade, a number of genomic, immunological, structural, and cell biology methodologies have been developed and used for determining the importance of apoE in the HCV life cycle. These methods and protocols will continue to be valuable to further understand the importance and the underlying molecular mechanism of various apolipoproteins in HCV infection and pathogenesis.

Key words

Apolipoprotein ApoE ApoB ApoC1 HCV Attachment Infectivity Morphogenesis 

Notes

Acknowledgment

This work was supported by NIH grants AI097318 and AI091953 and partially by the University of Alabama at Birmingham (UAB) Center for AIDS Research (CFAR), an NIH-funded program (P30 AI027767).

References

  1. 1.
    Andre P, Komurian-Pradel F, Deforges S, Perret M, Berland JL, Sodoyer M et al (2002) Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J Virol 76:6919–6928CrossRefGoogle Scholar
  2. 2.
    Andre P, Perlemuter G, Budkowska A, Brechot C, Lotteau V (2005) Hepatitis C virus particles and lipoprotein metabolism. Semin Liver Dis 25:93–104CrossRefGoogle Scholar
  3. 3.
    Hijikata M, Shimizu YK, Kato H, Iwamoto A, Shih JW, Alter HJ et al (1993) Equilibrium centrifugation studies of hepatitis C virus: evidence for circulating immune complexes. J Virol 67:1953–1958PubMedPubMedCentralGoogle Scholar
  4. 4.
    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 80:2418–2428CrossRefGoogle Scholar
  5. 5.
    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 181:293–300CrossRefGoogle Scholar
  6. 6.
    Thomssen R, Bonk S, Thiele A (1993) Density heterogeneities of hepatitis C virus in human sera due to the binding of beta-lipoproteins and immunoglobulins. Med Microbiol Immunol 182:329–334CrossRefGoogle Scholar
  7. 7.
    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 81:13783–13793CrossRefGoogle Scholar
  8. 8.
    Jiang J, Luo G (2009) Apolipoprotein E but not B is required for the formation of infectious hepatitis C virus particles. J Virol 83:12680–12691CrossRefGoogle Scholar
  9. 9.
    Meunier JC, Engle RE, Faulk K, Zhao M, Bartosch B, Alter H et al (2005) Evidence for cross-genotype neutralization of hepatitis C virus pseudo-particles and enhancement of infectivity by apolipoprotein C1. Proc Natl Acad Sci U S A 102:4560–4565CrossRefGoogle Scholar
  10. 10.
    Meunier JC, Russell RS, Engle RE, Faulk KN, Purcell RH, Emerson SU (2008) Apolipoprotein c1 association with hepatitis C virus. J Virol 82:9647–9656CrossRefGoogle Scholar
  11. 11.
    Nielsen SU, Bassendine MF, Martin C, Lowther D, Purcell PJ, King BJ et al (2008) Characterization of hepatitis C RNA-containing particles from human liver by density and size. J Gen Virol 89:2507–2517CrossRefGoogle Scholar
  12. 12.
    Maillard P, Huby T, Andreo U, Moreau M, Chapman J, Budkowska A (2006) The interaction of natural hepatitis C virus with human scavenger receptor SR-BI/Cla1 is mediated by ApoB-containing lipoproteins. FASEB J 20:735–737CrossRefGoogle Scholar
  13. 13.
    Cai Z, Zhang C, Chang KS, Jiang J, Ahn BC, Wakita T et al (2005) Robust production of infectious hepatitis C virus (HCV) from stably HCV cDNA-transfected human hepatoma cells. J Virol 79:13963–13973CrossRefGoogle Scholar
  14. 14.
    Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC et al (2005) Complete replication of hepatitis C virus in cell culture. Science 309:623–626CrossRefGoogle Scholar
  15. 15.
    Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z et al (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11:791–796CrossRefGoogle Scholar
  16. 16.
    Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR et al (2005) Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A 102:9294–9299CrossRefGoogle Scholar
  17. 17.
    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 82:2120–2129CrossRefGoogle Scholar
  18. 18.
    Huang H, Sun F, Owen DM, Li W, Chen Y, Gale M Jr et al (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 104:5848–5853CrossRefGoogle Scholar
  19. 19.
    Jammart B, Michelet M, Pecheur EI, Parent R, Bartosch B, Zoulim F et al (2013) Very-low-density lipoprotein (VLDL)-producing and hepatitis C virus-replicating HepG2 cells secrete no more lipoviroparticles than VLDL-deficient Huh7.5 cells. J Virol 87:5065–5080CrossRefGoogle Scholar
  20. 20.
    Benga WJ, Krieger SE, Dimitrova M, Zeisel MB, Parnot M, Lupberger J et al (2010) Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles. Hepatology 51:43–53CrossRefGoogle Scholar
  21. 21.
    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 84:11532–11541CrossRefGoogle Scholar
  22. 22.
    Jiang J, Cun W, Wu X, Shi Q, Tang H, Luo G (2012) Hepatitis C virus attachment mediated by apolipoprotein E binding to cell surface heparan sulfate. J Virol 86:7256–7267CrossRefGoogle Scholar
  23. 23.
    Jiang J, Wu X, Tang H, Luo G (2013) Apolipoprotein E mediates attachment of clinical hepatitis C virus to hepatocytes by binding to cell surface heparan sulfate proteoglycan receptors. PLoS One 8:e67982CrossRefGoogle Scholar
  24. 24.
    Shi Q, Jiang J, Luo G (2013) Syndecan-1 serves as the major receptor for attachment of hepatitis C virus to the surfaces of hepatocytes. J Virol 87:6866–6875CrossRefGoogle Scholar
  25. 25.
    Catanese MT, Uryu K, Kopp M, Edwards TJ, Andrus L, Rice WJ et al (2013) Ultrastructural analysis of hepatitis C virus particles. Proc Natl Acad Sci U S A 110:9505–9510CrossRefGoogle Scholar
  26. 26.
    Gastaminza P, Dryden KA, Boyd B, Wood MR, Law M, Yeager M et al (2010) Ultrastructural and biophysical characterization of hepatitis C virus particles produced in cell culture. J Virol 84:10999–11009CrossRefGoogle Scholar
  27. 27.
    Merz A, Long G, Hiet MS, Brugger B, Chlanda P, Andre P et al (2011) Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome. J Biol Chem 286:3018–3032CrossRefGoogle Scholar
  28. 28.
    Fan H, Qiao L, Kang KD, Fan J, Wei W, Luo G (2017) Attachment and postattachment receptors important for hepatitis C virus infection and cell-to-cell transmission. J Virol 91(13):e00280–e00217 In pressCrossRefGoogle Scholar
  29. 29.
    Liu S, McCormick KD, Zhao W, Zhao T, Fan D, Wang T (2012) Human apolipoprotein E peptides inhibit hepatitis C virus entry by blocking virus binding. Hepatology 56:484–491CrossRefGoogle Scholar
  30. 30.
    Lee JY, Acosta EG, Stoeck IK, Long G, Hiet MS, Mueller B et al (2014) Apolipoprotein E likely contributes to a maturation step of infectious hepatitis C virus particles and interacts with viral envelope glycoproteins. J Virol 88:12422–12437CrossRefGoogle Scholar
  31. 31.
    Bankwitz D, Doepke M, Hueging K, Weller R, Bruening J, Behrendt P et al (2017) Maturation of secreted HCV particles by incorporation of secreted ApoE protects from antibodies by enhancing infectivity. J Hepatol 67:480–489CrossRefGoogle Scholar
  32. 32.
    Fauvelle C, Felmlee DJ, Crouchet E, Lee J, Heydmann L, Lefevre M et al (2016) Apolipoprotein E mediates evasion from hepatitis C virus neutralizing antibodies. Gastroenterology 150:206–217 e204CrossRefGoogle Scholar
  33. 33.
    Wu X, Robotham JM, Lee E, Dalton S, Kneteman NM, Gilbert DM et al (2012) Productive hepatitis C virus infection of stem cell-derived hepatocytes reveals a critical transition to viral permissiveness during differentiation. PLoS Pathog 8:e1002617CrossRefGoogle Scholar
  34. 34.
    Jiang J, Luo G (2012) Cell culture-adaptive mutations promote viral protein-protein interactions and morphogenesis of infectious hepatitis C virus. J Virol 86:8987–8997CrossRefGoogle Scholar
  35. 35.
    Keck ZY, Xia J, Cai Z, Li TK, Owsianka AM, Patel AH et al (2007) Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions. J Virol 81:1043–1047CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MicrobiologyUniversity of Alabama at Birmingham School of MedicineBirminghamUSA

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