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

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

doi:10.1097/QAD.0000000000000963

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

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

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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.

Original language	English
Pages (from-to)	355-63
Number of pages	9
Journal	Aids
Volume	30
Issue number	3
DOIs	https://doi.org/10.1097/QAD.0000000000000963
Publication status	Published - 28 Jan 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1097/QAD.0000000000000963

Cite this

Goeser, F., Glässner, A., Kokordelis, P., Wolter, F., Lutz, P., Kaczmarek, D. J., Schwarze-Zander, C., Boesecke, C., Strassburg, C. P., Rockstroh, J. K., Spengler, U., Krämer, B., & Nattermann, J. (2016). HIV mono-infection is associated with an impaired anti-hepatitis C virus activity of natural killer cells. Aids, 30(3), 355-63. https://doi.org/10.1097/QAD.0000000000000963

@article{053fae31b7324bbfa7116996ea65d45b,

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

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.",

author = "Felix Goeser and Andreas Gl{\"a}ssner and Pavlos Kokordelis and Franziska Wolter and Philipp Lutz and Kaczmarek, {Dominik J} and Carolynne Schwarze-Zander and Christoph Boesecke and Strassburg, {Christian P} and Rockstroh, {J{\"u}rgen K} and Ulrich Spengler and Benjamin Kr{\"a}mer and Jacob Nattermann",

year = "2016",

month = jan,

day = "28",

doi = "10.1097/QAD.0000000000000963",

language = "English",

volume = "30",

pages = "355--63",

journal = "Aids",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "3",

}

Goeser, F, Glässner, A, Kokordelis, P, Wolter, F, Lutz, P, Kaczmarek, DJ, Schwarze-Zander, C, Boesecke, C, Strassburg, CP, Rockstroh, JK, Spengler, U, Krämer, B & Nattermann, J 2016, 'HIV mono-infection is associated with an impaired anti-hepatitis C virus activity of natural killer cells', Aids, vol. 30, no. 3, pp. 355-63. https://doi.org/10.1097/QAD.0000000000000963

TY - JOUR

T1 - HIV mono-infection is associated with an impaired anti-hepatitis C virus activity of natural killer cells

AU - Goeser, Felix

AU - Glässner, Andreas

AU - Kokordelis, Pavlos

AU - Wolter, Franziska

AU - Lutz, Philipp

AU - Kaczmarek, Dominik J

AU - Schwarze-Zander, Carolynne

AU - Boesecke, Christoph

AU - Strassburg, Christian P

AU - Rockstroh, Jürgen K

AU - Spengler, Ulrich

AU - Krämer, Benjamin

AU - Nattermann, Jacob

PY - 2016/1/28

Y1 - 2016/1/28

N2 - 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.

AB - 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.

U2 - 10.1097/QAD.0000000000000963

DO - 10.1097/QAD.0000000000000963

M3 - Article

C2 - 26558728

SN - 0269-9370

VL - 30

SP - 355

EP - 363

JO - Aids

JF - Aids

IS - 3

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this