Innate, non-cytolytic CD8+ T cell-mediated suppression of HIV replication by MHC-independent inhibition of virus transcription.
PLoS Pathog
; 16(9): e1008821, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32941545
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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Replicación Viral
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Antígenos de Histocompatibilidad Clase I
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VIH-1
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Linfocitos T CD8-positivos
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Inmunidad Innata
Límite:
Animals
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Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article