Innate, non-cytolytic CD8+ T cell-mediated suppression of HIV replication by MHC-independent inhibition of virus transcription.

Tytuł:: Innate, non-cytolytic CD8+ T cell-mediated suppression of HIV replication by MHC-independent inhibition of virus transcription.
Autorzy:: Zanoni M; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.
Palesch D; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.
Pinacchio C; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.
Statzu M; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.
Tharp GK; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.
Paiardini M; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.
Chahroudi A; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Bosinger SE; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.
Yoon J; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Cox B; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Silvestri G; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Kulpa DA; Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory Vaccine Center Emory University, Atlanta, Georgia, United States of America.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Źródło:: PLoS pathogens [PLoS Pathog] 2020 Sep 17; Vol. 16 (9), pp. e1008821. Date of Electronic Publication: 2020 Sep 17 (Print Publication: 2020).
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: San Francisco, CA : Public Library of Science, c2005-
MeSH Terms:: Immunity, Innate*
CD8-Positive T-Lymphocytes/*immunology
HIV-1/*physiology
Histocompatibility Antigens Class I/*immunology
Transcription, Genetic/*immunology
Virus Replication/*immunology
Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Cell Proliferation ; Humans ; Macaca
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Grant Information:: P30 AI050409 United States AI NIAID NIH HHS; P51 OD011132 United States OD NIH HHS; R01 AI143414 United States AI NIAID NIH HHS; R01 AI125064 United States AI NIAID NIH HHS; U42 OD011023 United States OD NIH HHS
Substance Nomenclature:: 0 (Histocompatibility Antigens Class I)
Entry Date(s):: Date Created: 20200917 Date Completed: 20201013 Latest Revision: 20210430
Update Code:: 20240104
PubMed Central ID:: PMC7523993
DOI:: 10.1371/journal.ppat.1008821
PMID:: 32941545
: Czasopismo naukowe

Pełny tekst

MHC-I-restricted, virus-specific cytotoxic CD8+ T cells (CTLs) may control human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication via the recognition and killing of productively infected CD4+ T cells. Several studies in SIV-infected macaques suggest that CD8+ T cells may also decrease virus production by suppressing viral transcription. Here, we show that non-HIV-specific, TCR-activated non-cytolytic CD8+ T cells suppress HIV transcription via a virus- and MHC-independent immunoregulatory mechanism that modulates CD4+ T cell proliferation and activation. We also demonstrate that this CD8+ T cell-mediated effect promotes the survival of infected CD4+ T cells harboring integrated, inducible virus. Finally, we used RNA sequencing and secretome analyses to identify candidate cellular pathways that are involved in the virus-silencing mediated by these CD8+ T cells. This study characterizes a previously undescribed mechanism of immune-mediated HIV silencing that may be involved in the establishment and maintenance of the reservoir under antiretroviral therapy and therefore represent a major obstacle to HIV eradication.
Competing Interests: The authors have declared that no competing interests exist.

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