Article thumbnail

Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein

By Stefania Crotta, Annalisa Stilla, Andreas Wack, Ra Nuti, Marta Mosca, Franco Filliponi, R. Maurizia Brunetto, Ferruccio Bonino, Sergio Abrignani and Nicholas M. Valiante

Abstract

The immune response against hepatitis C virus (HCV) is rarely effective at clearing the virus, resulting in �170 million chronic HCV infections worldwide. Here we report that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells. Cross-linking of CD81 by the major envelope protein of HCV (HCV-E2) or anti-CD81 antibodies blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation. This inhibitory effect was observed using both activated and resting NK cells. Conversely, on NK-like T cell clones, including those expressing NK cell inhibitory receptors, CD81 ligation delivered a costimulatory signal. Engagement of CD81 on NK cells blocks tyrosine phosphorylation through a mechanism which is distinct from the negative signaling pathways associated with NK cell inhibitory receptors for major histocompatibility complex class I. These results implicate HCV-E2–mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities of NK cells and allowing the virus to establish itself as a chronic infection. Key words: natural killer cells • inhibitory signaling • immune evasion • chronic viral infection • tetraspani

Year: 2002
OAI identifier: oai:CiteSeerX.psu:10.1.1.324.9492
Provided by: CiteSeerX
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://citeseerx.ist.psu.edu/v... (external link)
  • http://jem.rupress.org/content... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.