HIV mono-infection is associated with an impaired anti-hepatitis C virus activity of natural killer cells

Research output: Contribution to journalArticlepeer-review

Authors

  • Felix Goeser
  • Andreas Glässner
  • Pavlos Kokordelis
  • Franziska Wolter
  • Philipp Lutz
  • And 8 others
  • Dominik J Kaczmarek
  • Carolynne Schwarze-Zander
  • Christoph Boesecke
  • Christian P Strassburg
  • Jürgen K Rockstroh
  • Ulrich Spengler
  • Benjamin Krämer
  • Jacob Nattermann

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)355-63
Number of pages9
JournalAids
Volume30
Issue number3
Publication statusPublished - 28 Jan 2016