RT Journal Article
SR Electronic
T1 Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 128447
DO 10.1101/128447
A1 Sean Matthew McCauley
A1 Kyusik Kim
A1 Anetta Nowosielska
A1 Ann Dauphin
A1 William Edward Diehl
A1 Jeremy Luban
YR 2017
UL http://biorxiv.org/content/early/2017/08/07/128447.abstract
AB HIV-1-infected people who take antiviral drugs that render viremia undetectable have ongoing inflammation of unknown etiology. The HIV-1 provirus, a permanent genetic element in long-lived cells of the immune system, is not eliminated by antiviral drugs, and is therefore a possible contributor to this inflammation. Most HIV-1 proviruses in infected people are replication defective but many are transcriptionally active. We found that the HIV-1 provirus activated innate immune signaling in dendritic cells, macrophages, and CD4+ T cells. Immune activation required HIV-1 provirus transcription and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. If rev was provided in trans, all HIV-1 coding sequences were dispensable except those cis-acting sequences required for replication or splicing. These results indicate that Rev-dependent, intron-containing, HIV-1 RNA is detected by the innate immune system, and that drugs which inhibit HIV-1 transcription or Rev-dependent, HIV-1 RNA metabolism, would add qualitative benefit to current antiviral drug regimens.