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

Virology 2017 06 21;506:34-44. Epub 2017 Mar 21.

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2017.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505171PMC
June 2017
5 Reads

Publication Analysis

Top Keywords

asp rna
12
hiv-1 5'ltr
12
proviral latency
8
repressor complex
8
nucleosome assembly
8
jurkat cells
8
promoting nucleosome
8
polycomb repressor
8
hiv-1
7
latency
5
asp
5
hiv-1 replication
4
reduced hiv-1
4
rna reduced
4
histone h3k27me3
4
replication jurkat
4
expression asp
4
lysine histone
4
expression promoted
4
promoted establishment
4

Similar Publications