title: Hepatitis C virus infection upregulates CD55 expression on the hepatocyte surface and promotes association with virus particles.
abstract: CD55 limits excessive complement activation on the host cell surface by accelerating the decay of C3 convertases. In this study, we observed that hepatitis C virus (HCV) infection of hepatocytes or HCV core protein expression in transfected hepatocytes upregulated CD55 expression at the mRNA and protein levels. Further analysis suggested that the HCV core protein or full-length (FL) genome enhanced CD55 promoter activity in a luciferase-based assay, which was further augmented in the presence of interleukin-6. Mutation of the CREB or SP-1 binding site on the CD55 promoter impaired HCV core protein-mediated upregulation of CD55. HCV-infected or core protein-transfected Huh7.5 cells displayed greater viability in the presence of CD81 and CD55 antibodies and complement. Biochemical analysis revealed that CD55 was associated with cell culture-grown HCV after purification by sucrose density gradient ultracentrifugation. Consistent with this, a polyclonal antibody to CD55 captured cell culture-grown HCV. Blocking antibodies against CD55 or virus envelope glycoproteins in the presence of normal human serum as a source of complement inhibited HCV infection. The inhibition was enhanced in the presence of both the antibodies and serum complement. Collectively, these results suggest that HCV induces and associates with a negative regulator of the complement pathway, a likely mechanism for immune evasion.
authors: Department of Internal Medicine, St. Louis University, St. Louis, Missouri, USA.
authors: Budhaditya
authors: B
authors: Mazumdar
authors: Hangeun
authors: H
authors: Kim
authors: Keith
authors: K
authors: Meyer
authors: Sandip K
authors: SK
authors: Bose
authors: Adrian M
authors: AM
authors: Di Bisceglie
authors: Ratna B
authors: RB
authors: Ray
authors: Michael S
authors: MS
authors: Diamond
authors: John P
authors: JP
authors: Atkinson
authors: Ranjit
authors: R
authors: Ray
mesh_terms: D000704:Analysis of Variance; D000914:Antibodies, Viral / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003171:Complement Pathway, Classical / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008156:Luciferases; D060888:Real-Time Polymerase Chain Reaction; D014461:Ultracentrifugation; D014771:Virion / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D018958:CD55 Antigens; D017931:DNA Primers; D015850:Interleukin-6; D008156:Luciferases
references: Cancer Res. 2005 Feb 1;65(3):718-21
references: 15705866
references: Mol Immunol. 2007 Jan;44(1-3):73-81
references: 16884774
references: Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4675-9
references: 1711208
references: N Engl J Med. 2001 Apr 5;344(14):1058-66
references: 11287977
references: Virology. 2006 Jun 5;349(2):347-58
references: 16545852
references: Annu Rev Immunol. 1989;7:35-58
references: 2469439
references: Trends Immunol. 2002 Feb;23(2):61-4
references: 11929126
references: J Virol. 2009 Dec;83(24):12680-91
references: 19793818
references: J Biol Chem. 2003 Mar 21;278(12):10691-6
references: 12499389
references: PLoS One. 2011;6(8):e23699
references: 21887300
references: Annu Rev Immunol. 1991;9:431-55
references: 1910685
references: Nat Biotechnol. 2001 May;19(5):451-5
references: 11329015
references: Annu Rev Med. 2008;59:293-309
references: 17705684
references: Hepatology. 2012 Feb;55(2):354-63
references: 21932413
references: J Immunol. 1993 Jan 1;150(1):151-60
references: 7678027
references: Biochem J. 1989 Dec 1;264(2):581-8
references: 2481448
references: Clin Immunol. 2006 Feb-Mar;118(2-3):127-36
references: 16338172
references: Immunopharmacology. 1997 Dec;38(1-2):167-75
references: 9476128
references: Adv Immunol. 1996;61:201-83
references: 8834497
references: J Infect Dis. 2010 Sep 15;202(6):862-6
references: 20677942
references: J Virol. 2011 May;85(9):4157-66
references: 21345967
references: J Virol. 2006 May;80(9):4633-9
references: 16611923
references: J Gen Virol. 2003 Jan;84(Pt 1):1-15
references: 12533696
references: Semin Liver Dis. 1999;19(2):141-55
references: 10422197
references: Mol Immunol. 2004 Nov;41(11):1089-98
references: 15476920
references: Clin Exp Immunol. 2000 Aug;121(2):234-41
references: 10931136
references: Cancer Immunol Immunother. 2003 Oct;52(10):638-42
references: 12811528
references: Vaccine. 2008 Dec 30;26 Suppl 8:I15-21
references: 19388159
references: Adv Immunol. 2007;96:141-77
references: 17981206
references: Carcinogenesis. 2011 Aug;32(8):1190-7
references: 21665888
references: Br J Cancer. 1999 Aug;80(11):1820-5
references: 10468303
references: PLoS One. 2012;7(9):e45770
references: 23049856
references: J Virol. 2012 Feb;86(4):2221-8
references: 22171262
references: J Virol. 2012 Sep;86(17):8987-97
references: 22674987
references: Viruses. 2010 Sep;2(9):2108-33
references: 21994721
references: Virology. 2004 Feb 20;319(2):176-84
references: 15015499
references: Immunol Today. 1994 Feb;15(2):74-80
references: 7512342
references: Virology. 2000 May 25;271(1):197-204
references: 10814584
references: Int J Clin Lab Res. 1994;24(1):45-8
references: 8180423
references: J Virol. 2010 Apr;84(7):3210-9
references: 20071581
references: Virology. 2002 Jun 20;298(1):53-62
references: 12093173
references: Clin Cancer Res. 2008 Aug 1;14(15):4780-6
references: 18676748
references: Mol Immunol. 2009 Jul;46(11-12):2284-9
references: 19446335
references: J Med Virol. 2008 Jan;80(1):72-9
references: 18041021
references: Immunopharmacology. 2000 Aug;49(1-2):103-16
references: 10904110
references: Mol Immunol. 1990 Feb;27(2):197-201
references: 2157145