HIV mono-infection is associated with an impaired anti-hepatitis C virus activity of natural killer cells. (28th January 2016)

• Record Type: Journal Article
• Authors: Goeser, Felix; Glässner, Andreas; Kokordelis, Pavlos; Wolter, Franziska; Lutz, Philipp; Kaczmarek, Dominik J.; Schwarze-Zander, Carolynne; Boesecke, Christoph; Strassburg, Christian P.; Rockstroh, Jürgen K.; Spengler, Ulrich; Krämer, Benjamin; Nattermann, Jacob
• Is Part Of: AIDS. Volume 30:Number 3(2016)
• Publication Date: 2016-01-28
• Subjects: anti-hepatitis C virus activity -- CD4+ T cells -- hepatitis C virus -- hepatitis C virus replication -- HIV -- HuH7A2HCVreplicon cells -- natural killer cells; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000963
• Languages: English
• ISSNs: 0269-9370

Abstract

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 HuH7A2 HCVreplicon 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.