1887

Journal of General Virology header logo

Volume 90, Issue 5

Hepatitis C virus cell entry: role of lipoproteins and cellular receptors Free

Abstract

Hepatitis C virus (HCV), a major cause of chronic liver disease, is a single-stranded positive sense virus of the family . HCV cell entry is a multi-step process, involving several viral and cellular factors that trigger virus uptake into the hepatocyte. Tetraspanin CD81, human scavenger receptor SR-BI, and tight junction molecules Claudin-1 and occludin are the main receptors that mediate HCV entry. In addition, the virus may use glycosaminoglycans and/or low density receptors on host cells as initial attachment factors. A unique feature of HCV is the dependence of virus replication and assembly on host cell lipid metabolism. Most notably, during HCV assembly and release from the infected cells, virus particles associate with lipids and very-low-density lipoproteins. Thus, infectious virus circulates in patient sera in the form of triglyceride-rich particles. Consequently, lipoproteins and lipoprotein receptors play an essential role in virus uptake and the initiation of infection. This review summarizes the current knowledge about HCV receptors, mechanisms of HCV cell entry and the role of lipoproteins in this process.

  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.008300-0
2009-05-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/5/1055.html?itemId=/content/journal/jgv/10.1099/vir.0.008300-0&mimeType=html&fmt=ahah

References

  1. Acton S. L., Scherer P. E., Lodish H. F., Krieger M. 1994; Expression cloning of SR-BI, a CD36-related class B scavenger receptor. J Biol Chem 269:21003–21009
     [Google Scholar]
  2. Agnello V., Abel G., Elfahal M., Knight G. B., Zhang Q. X. 1999; Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A 96:12766–12771 [CrossRef]
     [Google Scholar]
  3. Akazawa D., Date T., Morikawa K., Murayama A., Miyamoto M., Kaga M., Barth H., Baumert T. F., Dubuisson J., Wakita T. 2007; CD81 expression is important for the permissiveness of Huh7 cell clones for heterogeneous hepatitis C virus infection. J Virol 81:5036–5045 [CrossRef]
     [Google Scholar]
  4. André P., Komurian-Pradel F., Deforges S., Perret M., Berland J. L., Sodoyer M., Pol S., Bréchot C., Paranhos-Baccalà G., Lotteau V. 2002; Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J Virol 76:6919–6928 [CrossRef]
     [Google Scholar]
  5. André P., Perlemuter G., Budkowska A., Bréchot C., Lotteau V. 2005; Hepatitis C virus particles and lipoprotein metabolism. Semin Liver Dis 25:93–104 [CrossRef]
     [Google Scholar]
  6. Andréo U., Maillard P., Kalinina O., Walic M., Meurs E., Martinot M., Marcellin P., Budkowska A. 2007; Lipoprotein lipase mediates hepatitis C virus (HCV) cell entry and inhibits HCV infection. Cell Microbiol 9:2445–2456 [CrossRef]
     [Google Scholar]
  7. Bartenschlager R., Sparacio S. 2007; Hepatitis C virus molecular clones and their replication capacity in vivo and in cell culture. Virus Res 127:195–207 [CrossRef]
     [Google Scholar]
  8. Bartenschlager R., Frese M., Pietschmann T. 2004; Novel insights into hepatitis C virus replication and persistence. Adv Virus Res 63:71–180
     [Google Scholar]
  9. Barth H., Schafer C., Adah M. I., Zhang F., Linhardt R. J., Toyoda H., Kinoshita-Toyoda A., Toida T., Van Kuppevelt T. H. other authors 2003; Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J Biol Chem 278:41003–41012 [CrossRef]
     [Google Scholar]
  10. Barth H., Ulsenheimer A., Pape G. R., Diepolder H. M., Hoffmann M., Neumann-Haefelin C., Thimme R., Henneke P., Klein R. other authors 2005; Uptake and presentation of hepatitis C virus-like particles by human dendritic cells. Blood 105:3605–3614 [CrossRef]
     [Google Scholar]
  11. Barth H., Liang T. J., Baumert T. F. 2006a; Hepatitis C virus entry: molecular biology and clinical implications. Hepatology 44:527–535 [CrossRef]
     [Google Scholar]
  12. Barth H., Schnober E. K., Zhang F., Linhardt R. J., Depla E., Boson B., Cosset F. L., Patel A. H., Blum H. E., Baumert T. F. 2006b; Viral and cellular determinants of the hepatitis C virus envelope-heparan sulfate interaction. J Virol 80:10579–10590 [CrossRef]
     [Google Scholar]
  13. Bartosch B., Dubuisson J., Cosset F. L. 2003a; Infectious hepatitis C virus pseudo-particles containing functional E1–E2 envelope protein complexes. J Exp Med 197:633–642 [CrossRef]
     [Google Scholar]
  14. Bartosch B., Vitelli A., Granier C., Goujon C., Dubuisson J., Pascale S., Scarselli E., Cortese R., Nicosia A., Cosset F. L. 2003b; Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. J Biol Chem 278:41624–41630 [CrossRef]
     [Google Scholar]
  15. Bartosch B., Verney G., Dreux M., Donot P., Morice Y., Penin F., Pawlotsky J. M., Lavillette D., Cosset F. L. 2005; An interplay between hypervariable region 1 of the hepatitis C virus E2 glycoprotein, the scavenger receptor BI, and high-density lipoprotein promotes both enhancement of infection and protection against neutralizing antibodies. J Virol 79:8217–8229 [CrossRef]
     [Google Scholar]
  16. Basu A., Kanda T., Beyene A., Saito K., Meyer K., Ray R. 2007; Sulfated homologues of heparin inhibit hepatitis C virus entry into mammalian cells. J Virol 81:3933–3941 [CrossRef]
     [Google Scholar]
  17. Baumert T. F., Ito S., Wong D. T., Liang T. J. 1998; Hepatitis C virus structural proteins assemble into virus-like particles in insect cells. J Virol 72:3827–3836
     [Google Scholar]
  18. Beach M. J., Meeks E. L., Mimms L. T., Vallari D., DuCharme L., Spelbring J., Taskar S., Schleicher J. B., Krawczynski K., Bradley D. W. 1992; Temporal relationships of hepatitis C virus RNA and antibody responses following experimental infection of chimpanzees. J Med Virol 36:226–237 [CrossRef]
     [Google Scholar]
  19. Benedicto I., Molina-Jiménez F., Barreiro O., Maldonado-Rodríguez A., Prieto J., Moreno-Otero R., Aldabe R., López-Cabrera M., Majano P. L. 2008; Hepatitis C virus envelope components alter localization of hepatocyte tight junction-associated proteins and promote occludin retention in the endoplasmic reticulum. Hepatology 48:1044–1053 [CrossRef]
     [Google Scholar]
  20. Bertaux C., Dragic T. 2006; Different domains of CD81 mediate distinct stages of hepatitis C virus pseudoparticle entry. J Virol 80:4940–4948 [CrossRef]
     [Google Scholar]
  21. Blanchard E., Belouzard S., Goueslain L., Wakita T., Dubuisson J., Wychowski C., Rouille Y. 2006; Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol 80:6964–6972 [CrossRef]
     [Google Scholar]
  22. Bradley D., McCaustland K., Krawczynski K., Spelbring J., Humphrey C., Cook E. H. 1991; Hepatitis C virus: buoyant density of the factor VIII-derived isolate in sucrose. J Med Virol 34:206–208 [CrossRef]
     [Google Scholar]
  23. Brass V., Moradpour D., Blum H. E. 2006; Molecular virology of hepatitis C virus (HCV): 2006 update. Int J Med Sci 3:29–34
     [Google Scholar]
  24. Brazzoli M., Bianchi A., Filippini S., Weiner A., Zhu Q., Pizza M., Crotta S. 2008; CD81 is a central regulator of cellular events required for hepatitis C virus infection of human hepatocytes. J Virol 82:8316–8329 [CrossRef]
     [Google Scholar]
  25. Bukh J., Purcell R. H. 2006; A milestone for hepatitis C virus research: a virus generated in cell culture is fully viable in vivo . Proc Natl Acad Sci U S A 103:3500–3501 [CrossRef]
     [Google Scholar]
  26. Cai L., de Beer M. C., de Beer F. C., van der Westhuyzen D. R. 2005; Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake. J Biol Chem 280:2954–2961 [CrossRef]
     [Google Scholar]
  27. Cai Z., Cai L., Jiang J., Chang K. S., van der Westhuyzen D. R., Luo G. 2007; Human serum amyloid A protein inhibits hepatitis C virus entry into cells. J Virol 81:6128–6133 [CrossRef]
     [Google Scholar]
  28. Callens N., Ciczora Y., Bartosch B., Vu-Dac N., Cosset F. L., Pawlotsky J. M., Penin F., Dubuisson J. 2005; Basic residues in hypervariable region 1 of hepatitis C virus envelope glycoprotein E2 contribute to virus entry. J Virol 79:15331–15341 [CrossRef]
     [Google Scholar]
  29. Calvo D., Vega M. A. 1993; Identification, primary structure, and distribution of CLA-1, a novel member of the CD36/LIMPII gene family. J Biol Chem 268:18929–18935
     [Google Scholar]
  30. Cambi A., Koopman M., Figdor C. G. 2005; How C-type lectins detect pathogens. Cell Microbiol 7:481–488 [CrossRef]
     [Google Scholar]
  31. Catanese M. T., Graziani R., von Hahn T., Moreau M., Huby T., Paonessa G., Santini C., Luzzago A., Rice C. M. other authors 2007; High-avidity monoclonal antibodies against the human scavenger class B type I receptor efficiently block hepatitis C virus infection in the presence of high-density lipoprotein. J Virol 81:8063–8071 [CrossRef]
     [Google Scholar]
  32. Chang K. S., 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 [CrossRef]
     [Google Scholar]
  33. Clayton R. F., Owsianka A., Aitken J., Graham S., Bhella D., Patel A. H. 2002; Analysis of antigenicity and topology of E2 glycoprotein present on recombinant hepatitis C virus-like particles. J Virol 76:7672–7682 [CrossRef]
     [Google Scholar]
  34. Cocquerel L., Wychowski C., Minner F., Penin F., Dubuisson J. 2000; Charged residues in the transmembrane domains of hepatitis C virus glycoproteins play a major role in the processing, subcellular localization, and assembly of these envelope proteins. J Virol 74:3623–3633 [CrossRef]
     [Google Scholar]
  35. Cocquerel L., Op de Beeck A., Lambot M., Roussel J., Delgrange D., Pillez A., Wychowski C., Penin F., Dubuisson J. 2002; Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins. EMBO J 21:2893–2902 [CrossRef]
     [Google Scholar]
  36. Cocquerel L., Voisset C., Dubuisson J. 2006; Hepatitis C virus entry: potential receptors and their biological functions. J Gen Virol 87:1075–1084 [CrossRef]
     [Google Scholar]
  37. Cormier E. G., Durso R. J., Tsamis F., Boussemart L., Manix C., Olson W. C., Gardner J. P., Dragic T. 2004a; L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus. Proc Natl Acad Sci U S A 101:14067–14072 [CrossRef]
     [Google Scholar]
  38. Cormier E. G., Tsamis F., Kajumo F., Durso R. J., Gardner J. P., Dragic T. 2004b; CD81 is an entry coreceptor for hepatitis C virus. Proc Natl Acad Sci U S A 101:7270–7274 [CrossRef]
     [Google Scholar]
  39. Coyne C. B., Bergelson J. M. 2006; Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. Cell 124:119–131 [CrossRef]
     [Google Scholar]
  40. Coyne C. B., Shen L., Turner J. R., Bergelson J. M. 2007; Coxsackievirus entry across epithelial tight junctions requires occludin and the small GTPases Rab34 and Rab5. Cell Host Microbe 2:181–192 [CrossRef]
     [Google Scholar]
  41. Cribier B., Schmitt C., Kirn A., Stoll-Keller F. 1998; Inhibition of hepatitis C virus adsorption to peripheral blood mononuclear cells by dextran sulfate. Arch Virol 143:375–379 [CrossRef]
     [Google Scholar]
  42. Crotta S., Stilla A., Wack A., D'Andrea A., Nuti S., D'Oro U., Mosca M., Filliponi F., Brunetto R. M. other authors 2002; Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein. J Exp Med 195:35–41 [CrossRef]
     [Google Scholar]
  43. Deleersnyder V., Pillez A., Wychowski C., Blight K., Xu J., Hahn Y. S., Rice C. M., Dubuisson J. 1997; Formation of native hepatitis C virus glycoprotein complexes. J Virol 71:697–704
     [Google Scholar]
  44. Diaz O., Delers F., Maynard M., Demignot S., Zoulim F., Chambaz J., Trépo C., Lotteau V., André P. 2006; Preferential association of hepatitis C virus with apolipoprotein B48-containing lipoproteins. J Gen Virol 87:2983–2991 [CrossRef]
     [Google Scholar]
  45. Dreux M., Pietschmann T., Granier C., Voisset C., Ricard-Blum S., Mangeot P. E., Keck Z., Foung S., Vu-Dac N. other authors 2006; High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI. J Biol Chem 281:18285–18295 [CrossRef]
     [Google Scholar]
  46. Dreux M., Boson B., Ricard-Blum S., Molle J., Lavillette D., Bartosch B., Pécheur E. I., Cosset F. L. 2007; The exchangeable apolipoprotein ApoC-I promotes membrane fusion of hepatitis C virus. J Biol Chem 282:32357–32369 [CrossRef]
     [Google Scholar]
  47. Drummer H. E., Wilson K. A., Poumbourios P. 2002; Identification of the hepatitis C virus E2 glycoprotein binding site on the large extracellular loop of CD81. J Virol 76:11143–11147 [CrossRef]
     [Google Scholar]
  48. Drummer H. E., Maerz A., Poumbourios P. 2003; Cell surface expression of functional hepatitis C virus E1 and E2 glycoproteins. FEBS Lett 546:385–390 [CrossRef]
     [Google Scholar]
  49. Drummer H. E., Wilson K. A., Poumbourios P. 2005; Determinants of CD81 dimerization and interaction with hepatitis C virus glycoprotein E2. Biochem Biophys Res Commun 328:251–257 [CrossRef]
     [Google Scholar]
  50. Dubuisson J. 2000; Folding, assembly and subcellular localization of hepatitis C virus glycoproteins. Curr Top Microbiol Immunol 242:135–148
     [Google Scholar]
  51. Evans M. J., von Hahn T., Tscherne D. M., Syder A. J., Panis M., Wölk B., Hatziioannou T., McKeating J. A., Bieniasz P. D., Rice C. M. 2007; Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446:801–805 [CrossRef]
     [Google Scholar]
  52. Flint M., Maidens C., Loomis-Price L. D., Shotton C., Dubuisson J., Monk P., Higginbottom A., Levy S., McKeating J. A. 1999; Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81. J Virol 73:6235–6244
     [Google Scholar]
  53. Flint M., von Hahn T., Zhang J., Farquhar M., Jones C. T., Balfe P., Rice C. M., McKeating J. A. 2006; Diverse CD81 proteins support hepatitis C virus infection. J Virol 80:11331–11342 [CrossRef]
     [Google Scholar]
  54. Forns X., Thimme R., Govindarajan S., Emerson S. U., Purcell R. H., Chisari F. V., Bukh J. 2000; Hepatitis C virus lacking the hypervariable region 1 of the second envelope protein is infectious and causes acute resolving or persistent infection in chimpanzees. Proc Natl Acad Sci U S A 97:13318–13323 [CrossRef]
     [Google Scholar]
  55. Fournier C., Sureau C., Coste J., Ducos J., Pageaux G., Larrey D., Domergue J., Maurel P. 1998; In vitro infection of adult normal human hepatocytes in primary culture by hepatitis C virus. J Gen Virol 79:2367–2374
     [Google Scholar]
  56. Fried M. W., Shiffman M. L., Reddy K. R., Smith C., Marinos G., Gonçales F. L. Jr, Häussinger D., Diago M., Carosi G. other authors 2002; Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347:975–982 [CrossRef]
     [Google Scholar]
  57. Furuse M., Hirase T., Itoh M., Nagafuchi A., Yonemura S., Tsukita S., Tsukita S. 1993; Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123:1777–1788 [CrossRef]
     [Google Scholar]
  58. Furuse M., Fujita K., Hiiragi T., Fujimoto K., Tsukita S. 1998; Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550 [CrossRef]
     [Google Scholar]
  59. Gardner J. P., Durso R. J., Arrigale R. R., Donovan G. P., Maddon P. J., Dragic T., Olson W. C. 2003; L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus. Proc Natl Acad Sci U S A 100:4498–4503 [CrossRef]
     [Google Scholar]
  60. Garry R. F., Dash S. 2003; Proteomics computational analyses suggest that hepatitis C virus E1 and pestivirus E2 envelope glycoproteins are truncated class II fusion proteins. Virology 307:255–265 [CrossRef]
     [Google Scholar]
  61. Gastaminza P., Kapadia S. B., Chisari F. V. 2006; Differential biophysical properties of infectious intracellular and secreted hepatitis C virus particles. J Virol 80:11074–11081 [CrossRef]
     [Google Scholar]
  62. Gastaminza P., Cheng G., Wieland S., Zhong J., Liao W., Chisari F. V. 2008; Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion. J Virol 82:2120–2129 [CrossRef]
     [Google Scholar]
  63. Germi R., Crance J. M., Garin D., Guimet J., Lortat-Jacob H., Ruigrok R. W., Zarski J. P., Drouet E. 2002; Cellular glycosaminoglycans and low density lipoprotein receptor are involved in hepatitis C virus adsorption. J Med Virol 68:206–215 [CrossRef]
     [Google Scholar]
  64. Goffard A., Callens N., Bartosch B., Wychowski C., Cosset F. L., Montpellier C., Dubuisson J. 2005; Role of N -linked glycans in the functions of hepatitis C virus envelope glycoproteins. J Virol 79:8400–8409 [CrossRef]
     [Google Scholar]
  65. Greber U. F., Gastaldelli M. 2007; Junctional gating: the Achilles' heel of epithelial cells in pathogen infection. Cell Host Microbe 2:143–146 [CrossRef]
     [Google Scholar]
  66. Grove J., Huby T., Stamataki Z., Vanwolleghem T., Meuleman P., Farquhar M., Schwarz A., Moreau M., Owen J. S. other authors 2007; Scavenger receptor BI and BII expression levels modulate hepatitis C virus infectivity. J Virol 81:3162–3169 [CrossRef]
     [Google Scholar]
  67. Haberstroh A., Schnober E. K., Zeisel M. B., Carolla P., Barth H., Blum H. E., Cosset F. L., Koutsoudakis G., Bartenschlager R. other authors 2008; Neutralizing host responses in hepatitis C virus infection target viral entry at postbinding steps and membrane fusion. Gastroenterology 135:1719–1728 [CrossRef]
     [Google Scholar]
  68. Helle F., Dubuisson J. 2008; Hepatitis C virus entry into host cells. Cell Mol Life Sci 65:100–112 [CrossRef]
     [Google Scholar]
  69. Helle F., Wychowski C., Vu-Dac N., Gustafson K. R., Voisset C., Dubuisson J. 2006; Cyanovirin-N inhibits hepatitis C virus entry by binding to envelope protein glycans. J Biol Chem 281:25177–25183 [CrossRef]
     [Google Scholar]
  70. Helle F., Goffard A., Morel V., Duverlie G., McKeating J., Keck Z. Y., Foung S., Penin F., Dubuisson J., Voisset C. 2007; The neutralizing activity of anti-hepatitis C virus antibodies is modulated by specific glycans on the E2 envelope protein. J Virol 81:8101–8111 [CrossRef]
     [Google Scholar]
  71. Hemler M. E. 2003; Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 19:397–422 [CrossRef]
     [Google Scholar]
  72. Higginbottom A., Quinn E. R., Kuo C. C., Flint M., Wilson L. H., Bianchi E., Nicosia A., Monk P. N., McKeating J. A., Levy S. 2000; Identification of amino acid residues in CD81 critical for interaction with hepatitis C virus envelope glycoprotein E2. J Virol 74:3642–3649 [CrossRef]
     [Google Scholar]
  73. Hsu M., Zhang J., Flint M., Logvinoff C., Cheng-Mayer C., Rice C. M., McKeating J. A. 2003; Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc Natl Acad Sci U S A 100:7271–7276 [CrossRef]
     [Google Scholar]
  74. Huang H., Sun F., Owen D. M., 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 [CrossRef]
     [Google Scholar]
  75. Jong M. C., Hofker M. H., Havekes L. M. 1999; Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3. Arterioscler Thromb Vasc Biol 19:472–484 [CrossRef]
     [Google Scholar]
  76. Kapadia S. B., Chisari F. V. 2005; Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci U S A 102:2561–2566 [CrossRef]
     [Google Scholar]
  77. Kapadia S. B., Barth H., Baumert T., McKeating J. A., Chisari F. V. 2007; Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I. J Virol 81:374–383 [CrossRef]
     [Google Scholar]
  78. Keam S. J., Cvetković R. S. 2008; Peginterferon- α -2a (40 kD) plus ribavirin: a review of its use in the management of chronic hepatitis C mono-infection. Drugs 68:1273–1317 [CrossRef]
     [Google Scholar]
  79. Keck Z. Y., Li T. K., Xia J., Gal-Tanamy M., Olson O., Li S. H., Patel A. H., Ball J. K., Lemon S. M., Foung S. K. 2008; Definition of a conserved immunodominant domain on hepatitis C virus E2 glycoprotein by neutralizing human monoclonal antibodies. J Virol 82:6061–6066 [CrossRef]
     [Google Scholar]
  80. Koutsoudakis G., Kaul A., Steinmann E., Kallis S., Lohmann V., Pietschmann T., Bartenschlager R. 2006; Characterization of the early steps of hepatitis C virus infection by using luciferase reporter viruses. J Virol 80:5308–5320 [CrossRef]
     [Google Scholar]
  81. Koutsoudakis G., Herrmann E., Kallis S., Bartenschlager R., Pietschmann T. 2007; The level of CD81 cell surface expression is a key determinant for productive entry of hepatitis C virus into host cells. J Virol 81:588–598 [CrossRef]
     [Google Scholar]
  82. Krieger M. 1999; Charting the fate of the “good cholesterol”: identification and characterization of the high-density lipoprotein receptor SR-BI. Annu Rev Biochem 68:523–558 [CrossRef]
     [Google Scholar]
  83. Larsson S. L., Skogsberg J., Bjorkegren J. 2004; The low density lipoprotein receptor prevents secretion of dense apoB100-containing lipoproteins from the liver. J Biol Chem 279:831–836 [CrossRef]
     [Google Scholar]
  84. Lavillette D., Tarr A. W., Voisset C., Donot P., Bartosch B., Bain C., Patel A. H., Dubuisson J., Ball J. K., Cosset F. L. 2005; Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology 41:265–274 [CrossRef]
     [Google Scholar]
  85. Lavillette D., Bartosch B., Nourrisson D., Verney G., Cosset F. L., Penin F., Pecheur E. I. 2006; Hepatitis C virus glycoproteins mediate low pH-dependent membrane fusion with liposomes. J Biol Chem 281:3909–3917 [CrossRef]
     [Google Scholar]
  86. Lavillette D., Pecheur E. I., Donot P., Fresquet J., Molle J., Corbau R., Dreux M., Penin F., Cosset F. L. 2007; Characterization of fusion determinants points to the involvement of three discrete regions of both E1 and E2 glycoproteins in the membrane fusion process of hepatitis C virus. J Virol 81:8752–8765 [CrossRef]
     [Google Scholar]
  87. Levy S., Shoham T. 2005; The tetraspanin web modulates immune-signalling complexes. Nat Rev Immunol 5:136–148 [CrossRef]
     [Google Scholar]
  88. Lindenbach B. D., Evans M. J., Syder A. J., Wölk B., Tellinghuisen T. L., Liu C. C., Maruyama T., Hynes R. O., Burton D. R. other authors 2005; Complete replication of hepatitis C virus in cell culture. Science 309:623–626 [CrossRef]
     [Google Scholar]
  89. Lindenbach B. D., Meuleman P., Ploss A., Vanwolleghem T., Syder A. J., McKeating J. A., Lanford R. E., Feinstone S. M., Major M. E. other authors 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 [CrossRef]
     [Google Scholar]
  90. Liu S., Yang W., Shen L., Turner J. R., Coyne C. B., Wang T. 2009; Tight junction proteins Claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J Virol 83:2011–2014 [CrossRef]
     [Google Scholar]
  91. Lozach P. Y., Amara A., Bartosch B., Virelizier J. L., Arenzana-Seisdedos F., Cosset F. L., Altmeyer R. 2004; C-type lectins L-SIGN and DC-SIGN capture and transmit infectious hepatitis C virus pseudotype particles. J Biol Chem 279:32035–32045 [CrossRef]
     [Google Scholar]
  92. Machida K., Cheng K. T., Pavio N., Sung V. M., Lai M. M. 2005; Hepatitis C virus E2–CD81 interaction induces hypermutation of the immunoglobulin gene in B cells. J Virol 79:8079–8089 [CrossRef]
     [Google Scholar]
  93. Maillard P., Krawczynski K., Nitkiewicz J., Bronnert C., Sidorkiewicz M., Gounon P., Dubuisson J., Faure G., Crainic R., Budkowska A. 2001; Nonenveloped nucleocapsids of hepatitis C virus in the serum of infected patients. J Virol 75:8240–8250 [CrossRef]
     [Google Scholar]
  94. Maillard P., Huby T., Andréo 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 20:735–737
     [Google Scholar]
  95. Manns M. P., McHutchison J. G., Gordon S. C., Rustgi V. K., Shiffman M., Reindollar R., Goodman Z. D., Koury K., Ling M., Albrecht J. K. 2001; Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358:958–965 [CrossRef]
     [Google Scholar]
  96. Masciopinto F., Giovani C., Campagnoli S., Galli-Stampino L., Colombatto P., Brunetto M., Yen T. S., Houghton M., Pileri P., Abrignani S. 2004; Association of hepatitis C virus envelope proteins with exosomes. Eur J Immunol 34:2834–2842 [CrossRef]
     [Google Scholar]
  97. Mead J. R., Irvine S. A., Ramji D. P. 2002; Lipoprotein lipase: structure, function, regulation, and role in disease. J Mol Med 80:753–769 [CrossRef]
     [Google Scholar]
  98. Meertens L., Bertaux C., Dragic T. 2006; Hepatitis C virus entry requires a critical postinternalization step and delivery to early endosomes via clathrin-coated vesicles. J Virol 80:11571–11578 [CrossRef]
     [Google Scholar]
  99. Meertens L., Bertaux C., Cukierman L., Cormier E., Lavillette D., Cosset F. L., Dragic T. 2008; The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus. J Virol 82:3555–3560 [CrossRef]
     [Google Scholar]
  100. Merkel M., Eckel R. H., Goldberg I. J. 2002; Lipoprotein lipase: genetics, lipid uptake, and regulation. J Lipid Res 43:1997–2006 [CrossRef]
     [Google Scholar]
  101. Meuleman P., Leroux-Roels G. 2008; The human liver-uPA-SCID mouse: a model for the evaluation of antiviral compounds against HBV and HCV. Antiviral Res 80:231–238 [CrossRef]
     [Google Scholar]
  102. Meuleman P., Libbrecht L., De Vos R., de Hemptinne B., Gevaert K., Vandekerckhove J., Roskams T., Leroux-Roels G. 2005; Morphological and biochemical characterization of a human liver in a uPA-SCID mouse chimera. Hepatology 41:847–856 [CrossRef]
     [Google Scholar]
  103. Meuleman P., Hesselgesser J., Paulson M., Vanwolleghem T., Desombere I., Reiser H., Leroux-Roels G. 2008; Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo . Hepatology 48:1761–1768 [CrossRef]
     [Google Scholar]
  104. Meunier J. C., Engle R. E., Faulk K., Zhao M., Bartosch B., Alter H., Emerson S. U., Cosset F. L., Purcell R. H., Bukh J. 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 102:4560–4565 [CrossRef]
     [Google Scholar]
  105. Meunier J. C., Russell R. S., Engle R. E., Faulk K. N., Purcell R. H., Emerson S. U. 2008; Apolipoprotein C1 association with hepatitis C virus. J Virol 82:9647–9656 [CrossRef]
     [Google Scholar]
  106. Michalak J. P., Wychowski C., Choukhi A., Meunier J. C., Ung S., Rice C. M., Dubuisson J. 1997; Characterization of truncated forms of hepatitis C virus glycoproteins. J Gen Virol 78:2299–2306
     [Google Scholar]
  107. Molina S., Castet V., Fournier-Wirth C., Pichard-Garcia L., Avner R., Harats D., Roitelman J., Barbaras R., Graber P. other authors 2007; The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus. J Hepatol 46:411–419 [CrossRef]
     [Google Scholar]
  108. Molina S., Castet V., Pichard-Garcia L., Wychowski C., Meurs E., Pascussi J. M., Sureau C., Fabre J. M., Sacunha A. other authors 2008a; Serum-derived hepatitis C virus infection of primary human hepatocytes is tetraspanin CD81 dependent. J Virol 82:569–574 [CrossRef]
     [Google Scholar]
  109. Molina S., Missé D., Roche S., Badiou S., Cristol J.-P., Bonfils C., Dierick J.-F., Veas F., Levayer T. other authors 2008b; Identification of apolipoprotein C-III as a potential plasmatic biomarker associated with the resolution of hepatitis C virus infection. Proteomics Clin Appl 2:751–761 [CrossRef]
     [Google Scholar]
  110. Monazahian M., Böhme I., Bonk S., Koch A., Scholz C., Grethe S., Thomssen R. 1999; Low density lipoprotein receptor as a candidate receptor for hepatitis C virus. J Med Virol 57:223–229 [CrossRef]
     [Google Scholar]
  111. Morikawa K., Zhao Z., Date T., Miyamoto M., Murayama A., Akazawa D., Tanabe J., Sone S., Wakita T. 2007; The roles of CD81 and glycosaminoglycans in the adsorption and uptake of infectious HCV particles. J Med Virol 79:714–723 [CrossRef]
     [Google Scholar]
  112. Murao K., Imachi H., Yu X., Cao W. M., Nishiuchi T., Chen K., Li J., Ahmed R. A., Wong N. C., Ishida T. 2008; Interferon α decreases expression of human scavenger receptor class BI, a possible HCV receptor in hepatocytes. Gut 57:664–671 [CrossRef]
     [Google Scholar]
  113. Nielsen S. U., Bassendine M. F., Burt A. D., Martin C., Pumeechockchai W., Toms G. L. 2006; Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients. J Virol 80:2418–2428 [CrossRef]
     [Google Scholar]
  114. Owsianka A., Clayton R. F., Loomis-Price L. D., McKeating J. A., Patel A. H. 2001; Functional analysis of hepatitis C virus E2 glycoproteins and virus-like particles reveals structural dissimilarities between different forms of E2. J Gen Virol 82:1877–1883
     [Google Scholar]
  115. Owsianka A. M., Timms J. M., Tarr A. W., Brown R. J., Hickling T. P., Szwejk A., Bienkowska-Szewczyk K., Thomson B. J., Patel A. H., Ball J. K. 2006; Identification of conserved residues in the E2 envelope glycoprotein of the hepatitis C virus that are critical for CD81 binding. J Virol 80:8695–8704 [CrossRef]
     [Google Scholar]
  116. Pawlotsky J. M. 2006; Therapy of hepatitis C: from empiricism to eradication. Hepatology 43:S207–S220 [CrossRef]
     [Google Scholar]
  117. Peng B. H., Lee J. C., Campbell G. A. 2003; In vitro protein complex formation with cytoskeleton-anchoring domain of occludin identified by limited proteolysis. J Biol Chem 278:49644–49651 [CrossRef]
     [Google Scholar]
  118. Penin F., Combet C., Germanidis G., Frainais P. O., Deléage G., Pawlotsky J. M. 2001; Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment. J Virol 75:5703–5710 [CrossRef]
     [Google Scholar]
  119. Penin F., Dubuisson J., Rey F. A., Moradpour D., Pawlotsky J. M. 2004; Structural biology of hepatitis C virus. Hepatology 39:5–19 [CrossRef]
     [Google Scholar]
  120. Pérez-Berná A. J., Bernabeu A., Moreno M. R., Guillen J., Villalaín J. 2008; The pre-transmembrane region of the HCV E1 envelope glycoprotein: interaction with model membranes. Biochim Biophys Acta 17782069–2080 [CrossRef]
     [Google Scholar]
  121. Peréz-Martínez P., Ordovàs J. M., López-Miranda J., Gómez P., Marín C., Moreno J., Fuentes F., Fernàndez de la Puebla R. A., Pérez-Jiménez F. 2003; Polymorphism exon 1 variant at the locus of the scavenger receptor class B type I gene: influence on plasma LDL cholesterol in healthy subjects during the consumption of diets with different fat contents. Am J Clin Nutr 77:809–813
     [Google Scholar]
  122. Petit J. M., Benichou M., Duvillard L., Jooste V., Bour J. B., Minello A., Verges B., Brun J. M., Gambert P., Hillon P. 2003; Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load, steatosis, and liver fibrosis. Am J Gastroenterol 98:1150–1154
     [Google Scholar]
  123. Petit M. A., Lièvre M., Peyrol S., De Sequeira S., Berthillon P., Ruigrok R. W., Trépo C. 2005; Enveloped particles in the serum of chronic hepatitis C patients. Virology 336:144–153 [CrossRef]
     [Google Scholar]
  124. Petit J. M., Minello A., Duvillard L., Jooste V., Monier S., Texier V., Bour J. B., Poussier A., Gambert P. other authors 2007; Cell surface expression of LDL receptor in chronic hepatitis C: correlation with viral load. Am J Physiol Endocrinol Metab 293:E416–E420 [CrossRef]
     [Google Scholar]
  125. Pileri P., Uematsu Y., Campagnoli S., Galli G., Falugi F., Petracca R., Weiner A. J., Houghton M., Rosa D. other authors 1998; Binding of hepatitis C virus to CD81. Science 282:938–941 [CrossRef]
     [Google Scholar]
  126. Ploss A., Evans M. J., Gaysinskaya V. A., Panis M., You H., de Jong Y. P., Rice C. M. 2009; Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 457:882–886 [CrossRef]
     [Google Scholar]
  127. Pöhlmann S., Zhang J., Baribaud F., Chen Z., Leslie G. J., Lin G., Granelli-Piperno A., Doms R. W., Rice C. M., McKeating J. A. 2003; Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. J Virol 77:4070–4080 [CrossRef]
     [Google Scholar]
  128. Prince A. M., Huima-Byron T., Parker T. S., Levine D. M. 1996; Visualization of hepatitis C virions and putative defective interfering particles isolated from low-density lipoproteins. J Viral Hepat 3:11–17 [CrossRef]
     [Google Scholar]
  129. Rhainds D., Brissette L. 2004; The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. defining the rules for lipid traders. Int J Biochem Cell Biol 36:39–77 [CrossRef]
     [Google Scholar]
  130. Roccasecca R., Ansuini H., Vitelli A., Meola A., Scarselli E., Acali S., Pezzanera M., Ercole B. B., McKeating J. other authors 2003; Binding of the hepatitis C virus E2 glycoprotein to CD81 is strain specific and is modulated by a complex interplay between hypervariable regions 1 and 2. J Virol 77:1856–1867 [CrossRef]
     [Google Scholar]
  131. Rocha-Perugini V., Montpellier C., Delgrange D., Wychowski C., Helle F., Pillez A., Drobecq H., Le Naour F., Charrin S. other authors 2008; The CD81 partner EWI-2wint inhibits hepatitis C virus entry. PLoS ONE 3:e1866 [CrossRef]
     [Google Scholar]
  132. Roohvand F., Maillard P., Lavergne J. P., Boulant S., Walic M., Andréo U., Goueslain L., Helle F., McLauchlan J., Budkowska A. 2009; Initiation of hepatitis C virus infection requires the dynamic microtubule network: Role of the viral nucleocapsid protein. J Biol Chem (in press). doi: 10.1074/jbc.M807873200
    [Google Scholar]
  133. Rudenko G., Deisenhofer J. 2003; The low-density lipoprotein receptor: ligands, debates and lore. Curr Opin Struct Biol 13:683–689 [CrossRef]
     [Google Scholar]
  134. Rumin S., Berthillon P., Tanaka E., Kiyosawa K., Trabaud M. A., Bizollon T., Gouillat C., Gripon P., Guguen-Guillouzo C. other authors 1999; Dynamic analysis of hepatitis C virus replication and quasispecies selection in long-term cultures of adult human hepatocytes infected in vitro . J Gen Virol 80:3007–3018
     [Google Scholar]
  135. Saunier B., Triyatni M., Ulianich L., Maruvada P., Yen P., Kohn L. D. 2003; Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol 77:546–559 [CrossRef]
     [Google Scholar]
  136. Scarselli E., Ansuini H., Cerino R., Roccasecca R. M., Acali S., Filocamo G., Traboni C., Nicosia A., Cortese R., Vitelli A. 2002; The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21:5017–5025 [CrossRef]
     [Google Scholar]
  137. Shelness G. S., Sellers J. A. 2001; Very-low-density lipoprotein assembly and secretion. Curr Opin Lipidol 12:151–157 [CrossRef]
     [Google Scholar]
  138. Shepard C. W., Finelli L., Alter M. J. 2005; Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 5:558–567 [CrossRef]
     [Google Scholar]
  139. Shimizu Y. K., Iwamoto A., Hijikata M., Purcell R. H., Yoshikura H. 1992; Evidence for in vitro replication of hepatitis C virus genome in a human T-cell line. Proc Natl Acad Sci U S A 89:5477–5481 [CrossRef]
     [Google Scholar]
  140. Shin K., Fogg V. C., Margolis B. 2006; Tight junctions and cell polarity. Annu Rev Cell Dev Biol 22:207–235 [CrossRef]
     [Google Scholar]
  141. Shoham T., Rajapaksa R., Kuo C. C., Haimovich J., Levy S. 2006; Building of the tetraspanin web: distinct structural domains of CD81 function in different cellular compartments. Mol Cell Biol 26:1373–1385 [CrossRef]
     [Google Scholar]
  142. Steinmann E., Whitfield T., Kallis S., Dwek R. A., Zitzmann N., Pietschmann T., Bartenschlager R. 2007; Antiviral effects of amantadine and iminosugar derivatives against hepatitis C virus. Hepatology 46:330–338
     [Google Scholar]
  143. Stockert R. J. 1995; The asialoglycoprotein receptor: relationships between structure, function, and expression. Physiol Rev 75:591–609
     [Google Scholar]
  144. Subramanian V. S., Marchant J. S., Ye D., Ma T. Y., Said H. M. 2007; Tight junction targeting and intracellular trafficking of occludin in polarized epithelial cells. Am J Physiol Cell Physiol 293:C1717–C1726 [CrossRef]
     [Google Scholar]
  145. Swarnakar S., Temel R. E., Connelly M. A., Azhar S., Williams D. L. 1999; Scavenger receptor class B, type I, mediates selective uptake of low density lipoprotein cholesteryl ester. J Biol Chem 274:29733–29739 [CrossRef]
     [Google Scholar]
  146. Thomssen R., Bonk S., Propfe C., Heermann K. H., Köchel H. G., Uy A. 1992; Association of hepatitis C virus in human sera with β -lipoprotein. Med Microbiol Immunol 181:293–300 [CrossRef]
     [Google Scholar]
  147. Triyatni M., Saunier B., Maruvada P., Davis A. R., Ulianich L., Heller T., Patel A., Kohn L. D., Liang T. J. 2002; Interaction of hepatitis C virus-like particles and cells: a model system for studying viral binding and entry. J Virol 76:9335–9344 [CrossRef]
     [Google Scholar]
  148. Uhlar C. M., Whitehead A. S. 1999; Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem 265:501–523 [CrossRef]
     [Google Scholar]
  149. Van Eck M., Hoekstra M., Out R., Bos I. S., Kruijt J. K., Hildebrand R. B., Van Berkel T. J. 2008; Scavenger receptor BI facilitates the metabolism of VLDL lipoproteins in vivo . J Lipid Res 49:136–146 [CrossRef]
     [Google Scholar]
  150. Van Itallie C. M., Anderson J. M. 2004; The molecular physiology of tight junction pores. Physiology (Bethesda) 19:331–338 [CrossRef]
     [Google Scholar]
  151. Van Itallie C. M., Anderson J. M. 2006; Claudins and epithelial paracellular transport. Annu Rev Physiol 68:403–429 [CrossRef]
     [Google Scholar]
  152. Van Kooyk Y., Geijtenbeek T. B. 2003; DC-SIGN: escape mechanism for pathogens. Nat Rev Immunol 3:697–709 [CrossRef]
     [Google Scholar]
  153. Voisset C., Callens N., Blanchard E., Op De Beeck A., Dubuisson J., Vu-Dac N. 2005; High density lipoproteins facilitate hepatitis C virus entry through the scavenger receptor class B type I. J Biol Chem 280:7793–7799 [CrossRef]
     [Google Scholar]
  154. von Hahn T., Rice C. M. 2008; Hepatitis C virus entry. J Biol Chem 283:3689–3693 [CrossRef]
     [Google Scholar]
  155. von Hahn T., Lindenbach B. D., Boullier A., Quehenberger O., Paulson M., Rice C. M., McKeating J. A. 2006; Oxidized low-density lipoprotein inhibits hepatitis C virus cell entry in human hepatoma cells. Hepatology 43:932–942 [CrossRef]
     [Google Scholar]
  156. von Hahn T., Yoon J. C., Alter H., Rice C. M., Rehermann B., Balfe P., McKeating J. A. 2007; Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo . Gastroenterology 132:667–678 [CrossRef]
     [Google Scholar]
  157. Wack A., Soldaini E., Tseng C., Nuti S., Klimpel G., Abrignani S. 2001; Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells. Eur J Immunol 31:166–175 [CrossRef]
     [Google Scholar]
  158. Wakita T., Pietschmann T., Kato T., Date T., Miyamoto M., Zhao Z., Murthy K., Habermann A., Kräusslich H. G. other authors 2005; Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11:791–796 [CrossRef]
     [Google Scholar]
  159. Yalaoui S., Huby T., Franetich J. F., Gego A., Rametti A., Moreau M., Collet X., Siau A., van Gemert G. J. other authors 2008; Scavenger receptor BI boosts hepatocyte permissiveness to Plasmodium infection. Cell Host Microbe 4:283–292 [CrossRef]
     [Google Scholar]
  160. Yang W., Qiu C., Biswas N., Jin J., Watkins S. C., Montelaro R. C., Coyne C. B., Wang T. 2008; Correlation of the tight junction-like distribution of Claudin-1 to the cellular tropism of hepatitis C virus. J Biol Chem 283:8643–8653 [CrossRef]
     [Google Scholar]
  161. Ye J. 2007; Reliance of host cholesterol metabolic pathways for the life cycle of hepatitis C virus. PLoS Pathog 3:e108 [CrossRef]
     [Google Scholar]
  162. Ye J., Wang C., Sumpter R. Jr, Brown M. S., Goldstein J. L., Gale M. Jr 2003; Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci U S A 100:15865–15870 [CrossRef]
     [Google Scholar]
  163. Zeisel M. B., Koutsoudakis G., Schnober E. K., Haberstroh A., Blum H. E., Cosset F. L., Wakita T., Jaeck D., Doffoel M. other authors 2007; Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81. Hepatology 46:1722–1731 [CrossRef]
     [Google Scholar]
  164. Zhang J., Randall G., Higginbottom A., Monk P., Rice C. M., McKeating J. A. 2004; CD81 is required for hepatitis C virus glycoprotein-mediated viral infection. J Virol 78:1448–1455 [CrossRef]
     [Google Scholar]
  165. Zheng A., Yuan F., Li Y., Zhu F., Hou P., Li J., Song X., Ding M., Deng H. 2007; Claudin-6 and Claudin-9 function as additional coreceptors for hepatitis C virus. J Virol 81:12465–12471 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.008300-0
Loading
Hepatitis C virus cell entry: role of lipoproteins and cellular receptors
J. Gen. Virol. 90, 1055 (2009); https://doi.org/10.1099/vir.0.008300-0
/content/journal/jgv/10.1099/vir.0.008300-0
/content/journal/jgv/10.1099/vir.0.008300-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error