Pegylated Interferon-α-Induced Natural Killer Cell Activation Is Associated With Human Immunodeficiency Virus-1 DNA Decline in Antiretroviral Therapy-Treated HIV-1/Hepatitis C Virus-Coinfected Patients.

Autor:	Hua S; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge., Vigano S; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge., Tse S; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge., Zhengyu O; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge., Harrington S; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge., Negron J; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge., Garcia-Broncano P; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge.; Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, Madrid, Spain., Marchetti G; Department of Health Sciences, Clinic of Infectious and Tropical Diseases, San Paolo Hospital, University of Milan, Italy., Genebat M; Laboratory of Immunovirology, University of Seville, Spain., Leal M; Laboratory of Immunovirology, University of Seville, Spain., Resino S; Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, Madrid, Spain., Ruiz-Mateos E; Laboratory of Immunovirology, University of Seville, Spain.; Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/Spanish National Research Council (CSIC)/University of Seville, Spain., Lichterfeld M; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge.; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Yu XG; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge.; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2018 Jun 01; Vol. 66 (12), pp. 1910-1917.
DOI:	10.1093/cid/cix1111
Abstrakt:	Background: Interferon alpha (IFN-α) can potently reduce human immunodeficiency virus type 1 (HIV-1) replication in tissue culture and animal models, but may also modulate residual viral reservoirs that persist despite suppressive antiretroviral combination therapy. However, mechanisms leading to viral reservoir reduction during IFN-α treatment are unclear. Methods: We analyzed HIV-1 gag DNA levels in CD4 T cells by digital droplet polymerase chain reaction and CD8 T-cell and natural killer (NK) cell phenotypes by flow cytometry in a cohort of antiretroviral therapy-treated HIV-1/hepatitis C virus-coinfected patients (n = 67) undergoing treatment for hepatitis C infection with pegylated IFN-α and ribavirin for an average of 11 months. Results: We observed that IFN-α treatment induced a significant decrease in CD4 T-cell counts (P < .0001), in CD4 T-cell-associated HIV-1 DNA copies (P = .002) and in HIV-1 DNA copies per microliter of blood (P < .0001) in our study patients. Notably, HIV-1 DNA levels were unrelated to HIV-1-specific CD8 T-cell responses. In contrast, proportions of total NK cells, CD56brightCD16- NK cells, and CD56brightCD16+ NK cells were significantly correlated with reduced levels of CD4 T-cell-associated HIV-1 DNA during IFN-α treatment, especially when coexpressing the activation markers NKG2D and NKp30. Conclusions: These data suggest that the reduction of viral reservoir cells during treatment with IFN-α is primarily attributable to antiviral activities of NK cells.
Databáze:	MEDLINE
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