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Nat Commun. 2018 Dec 13;9(1):5305. doi: 10.1038/s41467-018-07753-2.

Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines.

Author information

1
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
2
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA. jeremy.luban@umassmed.edu.
3
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA. jeremy.luban@umassmed.edu.

Abstract

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, HIV-1 establishes proviruses in long-lived CD4+ memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Here we show that the HIV-1 provirus activates innate immune signaling in isolated dendritic cells, macrophages, and CD4+ T cells. Immune activation requires transcription from the HIV-1 provirus and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. If rev is provided in trans, all HIV-1 coding sequences are dispensable for activation except those cis-acting sequences required for replication or splicing. Our results indicate that the complex, post-transcriptional regulation intrinsic to HIV-1 RNA is detected by the innate immune system as a danger signal, and that drugs which disrupt HIV-1 transcription or HIV-1 RNA metabolism would add qualitative benefit to current antiviral drug regimens.

PMID:
30546110
PMCID:
PMC6294009
DOI:
10.1038/s41467-018-07753-2
[Indexed for MEDLINE]
Free PMC Article

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