The Human Immunodeficiency Virus 1 ASP RNA promotes viral latency by recruiting the Polycomb Repressor Complex 2 and promoting nucleosome assembly.
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.
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Juan C
JC
Zapata
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Federica
F
Campilongo
Laboratory of Molecular Virology, George Mason University, Manassas, VA, USA.
Robert A
RA
Barclay
Laboratory of Molecular Virology, George Mason University, Manassas, VA, USA.
Catherine
C
DeMarino
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Maria D
MD
Iglesias-Ussel
Laboratory of Molecular Virology, George Mason University, Manassas, VA, USA.
Fatah
F
Kashanchi
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: fromerio@ihv.umaryland.edu.
Fabio
F
Romerio
D042002:Chromatin Assembly and Disassembly; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral; D017735:Virus Latency
D006657:Histones; D009707:Nucleosomes; D016372:RNA, Antisense; D012367:RNA, Viral; D063151:Polycomb Repressive Complex 2
ASP; Antisense transcript; Epigenetic marks; H3K27me3; HIV-1; PRC2; Viral latency