HIV Mono-Infection Is Associated With an Impaired Anti-Hepatitis C Virus Activity of Natural Killer Cells

AIDS. 2016 Jan 28;30(3):355-63. doi: 10.1097/QAD.0000000000000963.

Abstract

Objective: Hepatitis C virus (HCV) infection in HIV(+) patients is associated with faster liver disease progression compared with HCV mono-infection. HIV-associated immune defects are considered to play an important role in this context. Here, we analyzed the effects of HIV infection on natural killer (NK)-cell-mediated anti-HCV activity.

Design: NK cell phenotype and interferon gamma (IFN-γ) production, NK cell-mediated inhibition of HCV replication and CD4 T-cell/NK cell interactions were studied in treatment naive HIV (n = 22), and HIV patients under combined antiretroviral therapy (n = 29), compared with healthy controls (n = 20).

Methods: NK cell-mediated inhibition of HCV replication was analyzed using the HuH7A2HCVreplicon model. IFN-γ production of NK cells as well as interleukin-2 secretion of CD4 T lymphocytes were studied by flow cytometry.

Results: Peripheral blood mononuclear cells from HIV(+) patients displayed a significantly impaired anti-HCV activity, irrespective of combined antiretroviral therapy. This could in part be explained by HIV-associated decline in NK cell numbers. In addition, NK cell IFN-γ production was significantly impaired in HIV infection. Accordingly, we found low frequency of IFN-γ(+) NK cells in HIV(+) patients to be associated with ineffective inhibition of HCV replication. Finally, we show that CD4 T-cell-mediated stimulation of NK cell IFN-γ production was dysregulated in HIV infection with an impaired interleukin-2 response of NK cells.

Conclusion: HIV infection has a strong suppressive effect on anti-HCV activity of NK cells. This may contribute to low spontaneous clearance rate and accelerated progression of HCV-associated liver disease observed in HIV(+) patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Hepacivirus / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Killer Cells, Natural / immunology*
  • Male
  • Middle Aged

Substances

  • Anti-Retroviral Agents
  • Interleukin-2
  • Interferon-gamma