Binding of the hepatitis C virus envelope protein E2 to CD81 inhibits natural killer cell functions

Chien-Te Tseng, Gary R. Klimpel

Research output: Contribution to journalArticle

369 Citations (Scopus)

Abstract

Infection with hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. Little is known about how this virus is able to persist or whether this persistence might be because of its ability to alter the early innate immune response. The major HCV envelope protein E2 has been shown to bind to CD81. Thus, HCV binding to natural killer (NK) cells could result in the cross-linking of CD81. To explore this possibility, we investigated whether cross-linking CD81 on NK cells could alter NK cell function. CD81 cross-linking by monoclonal antibody (mAb) specific for CD81 or by immobilized E2 have been shown to result in costimulatory signals for human T cells. In this study, we show that CD81 cross-linking via immobilized E2 or mAbs specific for CD81 inhibits not only non major histocompatibility complex-restricted cytotoxicity mediated by NK cells but also interferon (IFN)-γ production by NK cells after exposure to interleukin (IL)-2, IL-12, IL-15, or CD16 cross-linking. These results show that CD81 cross-linking mediates completely different signals in NK cells versus T cells. Importantly, these results suggest that one mechanism whereby HCV can alter host defenses and innate immunity is via-the early inhibition of IFN-γ production by NK cells.

Original languageEnglish (US)
Pages (from-to)43-49
Number of pages7
JournalJournal of Experimental Medicine
Volume195
Issue number1
DOIs
StatePublished - Jan 7 2002

Fingerprint

Viral Envelope Proteins
Natural Killer Cells
Hepacivirus
Innate Immunity
Interferons
T-Lymphocytes
Virus Attachment
Interleukin-15
Interleukin-12
Major Histocompatibility Complex
Interleukin-2
Liver Diseases
Chronic Disease
Monoclonal Antibodies
Viruses
Infection

Keywords

  • Cytokines
  • Hepatitis C virus
  • NK cells
  • Virus

ASJC Scopus subject areas

  • Immunology

Cite this

Binding of the hepatitis C virus envelope protein E2 to CD81 inhibits natural killer cell functions. / Tseng, Chien-Te; Klimpel, Gary R.

In: Journal of Experimental Medicine, Vol. 195, No. 1, 07.01.2002, p. 43-49.

Research output: Contribution to journalArticle

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