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HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response in CD4 + T Cells.
- Source :
-
Cell reports [Cell Rep] 2016 Oct 04; Vol. 17 (2), pp. 413-424. - Publication Year :
- 2016
-
Abstract
- Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4 <superscript>+</superscript> T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction. Furthermore, Vpr also amplifies innate sensing of HIV-1 infection in Vpx-treated dendritic cells. Our results identify cGAS as mediator of an IFN-I response to HIV-1 infection in CD4 <superscript>+</superscript> T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cells of HIV-1.<br /> (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes virology
Dendritic Cells immunology
Dendritic Cells metabolism
Dendritic Cells virology
HEK293 Cells
HIV Infections genetics
HIV Infections virology
HIV-1 immunology
HIV-1 pathogenicity
Human Immunodeficiency Virus Proteins immunology
Humans
Immunity, Innate genetics
Interferon Type I genetics
Lentivirus genetics
Nucleotidyltransferases immunology
Viral Regulatory and Accessory Proteins immunology
vpr Gene Products, Human Immunodeficiency Virus immunology
HIV Infections immunology
Human Immunodeficiency Virus Proteins genetics
Interferon Type I immunology
Nucleotidyltransferases genetics
Viral Regulatory and Accessory Proteins genetics
vpr Gene Products, Human Immunodeficiency Virus genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 27705790
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.09.023