The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus replication through interferon gamma-inducible protein-10

BMC Immunol. 2012 Apr 3:13:15. doi: 10.1186/1471-2172-13-15.

Abstract

Background: Co-infection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) is associated with faster progression of liver disease and an increase in HCV persistence. However, the mechanism by which HIV-1 accelerates the progression of HCV liver disease remains unknown.

Results: HIV-1/HCV co-infection is associated with increased expression of interferon gamma-induced protein-10 (IP-10) mRNA in peripheral blood mononuclear cells (PBMCs). HCV RNA levels were higher in PBMCs of patients with HIV-1/HCV co-infection than in patients with HCV mono-infection. HIV-1 Tat and IP-10 activated HCV replication in a time-dependent manner, and HIV-1 Tat induced IP-10 production. In addition, the effect of HIV-1 Tat on HCV replication was blocked by anti-IP-10 monoclonal antibody, demonstrating that the effect of HIV-1 Tat on HCV replication depends on IP-10. Taken together, these results suggest that HIV-1 Tat protein activates HCV replication by upregulating IP-10 production.

Conclusions: HIV-1/HCV co-infection is associated with increased expression of IP-10 mRNA and replication of HCV RNA. Furthermore, both HIV-1 Tat and IP-10 activate HCV replication. HIV-1 Tat activates HCV replication by upregulating IP-10 production. These results expand our understanding of HIV-1 in HCV replication and the mechanism involved in the regulation of HCV replication mediated by HIV-1 during co-infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology
  • Antibodies / metabolism
  • Cell Line
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL10 / metabolism*
  • Coinfection
  • HIV Infections / genetics
  • HIV Infections / virology
  • HIV-1 / metabolism*
  • Hepacivirus / metabolism
  • Hepacivirus / physiology*
  • Hepatitis C / genetics
  • Hepatitis C / virology
  • Humans
  • RNA, Viral / blood
  • Virus Replication*
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Antibodies
  • Chemokine CXCL10
  • RNA, Viral
  • tat Gene Products, Human Immunodeficiency Virus