The Human Immunodeficiency Virus 1 ASP RNA promotes viral latency by recruiting the Polycomb Repressor Complex 2 and promoting nucleosome assembly.

Published

Journal Article

Various epigenetic marks at the HIV-1 5'LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3'LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells. Moreover, ASP RNA expression promoted the establishment and maintenance of HIV-1 latency in Jurkat E4 cells. We show that this transcript interacts with and recruits PRC2 to the HIV-1 5'LTR, increasing accumulation of the suppressive epigenetic mark H3K27me3, while reducing RNA Polymerase II and thus proviral transcription. Altogether, our results suggest that the HIV-1 ASP transcript promotes epigenetic silencing of the HIV-1 5'LTR and proviral latency through the PRC2 pathway.

Full Text

Duke Authors

Cited Authors

  • Zapata, JC; Campilongo, F; Barclay, RA; DeMarino, C; Iglesias-Ussel, MD; Kashanchi, F; Romerio, F

Published Date

  • June 2017

Published In

Volume / Issue

  • 506 /

Start / End Page

  • 34 - 44

PubMed ID

  • 28340355

Pubmed Central ID

  • 28340355

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

International Standard Serial Number (ISSN)

  • 2514-4138

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2017.03.002

Language

  • eng