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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

McCauley SM,Kim K,Nowosielska A,Dauphin A,Yurkovetskiy L,Diehl WE,Luban J

doi

10.1038/s41467-018-07753-2

subject

Has Abstract

pub_date

2018-12-13 00:00:00

pages

5305

issue

1

issn

2041-1723

pii

10.1038/s41467-018-07753-2

journal_volume

9

pub_type

杂志文章

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