Suv39H1 and HP1γ are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency

Abstract

HIV‐1 gene expression is the major determinant regulating the rate of virus replication and, consequently, AIDS progression. Following primary infection, most infected cells produce virus. However, a small population becomes latently infected and constitutes the viral reservoir. This stable viral reservoir seriously challenges the hope of complete viral eradication. Viewed in this context, it is critical to define the molecular mechanisms involved in the establishment of transcriptional latency and the reactivation of viral expression. We show that Suv39H1, HP1γ and histone H3Lys9 trimethylation play a major role in chromatin‐mediated repression of integrated HIV‐1 gene expression. Suv39H1, HP1γ and histone H3Lys9 trimethylation are reversibly associated with HIV‐1 in a transcription‐dependent manner. Finally, we show in different cellular models, including PBMCs from HIV‐1‐infected donors, that HIV‐1 reactivation could be achieved after HP1γ RNA interference.

Transcriptional Derepression of the ERVWE1 Locus following Influenza A Virus Infection

“…Proviral silencing also involves dimethylation of H3K9 through KMTase G9a (61). In addition, du Chene et al reported that enrichment of H3K9me3 and transcriptional repression of integrated HIV-1 LTRs involve recruitment of the KMTase SUV39H1 (63). It remains to be established whether these factors are also involved in the expression of HERV-W during virus infection.…”

Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

“…This is consistent with H3K27me3 being generally a more flexible epigenetic repressive mark and with the likelihood that most of the inducible latent provirus is silenced through pathways involving H3K27me3, rather than H3K9me3. H3K9me3 has only been found in a few HIV-1 latency studies and re-activation of latent provirus carrying this mark has either not been observed after strong stimulation (with Phorbol-Myristate-Acetate treatment) or has required silencing of HP1-γ or other factors through RNAi [178,179] . This supports H3K9me3 as a more robust repressive epigenetic mark.…”

A Novel Role for PA28γ-Proteasome in Nuclear Speckle Organization and SR Protein Trafficking

“…For this purpose, we used the 2E11 (also called pU2OS_Exo1) cell line, that harbors an integrated inducible HIV-1 reporter gene containing a splice site for SF2/ASF. An additional RNA tag (MS2) was inserted to facilitate its visualization by in situ hybridization (Boireau et al, 2007;du Chéné et al, 2007). The ability of SF2/ASF to be recruited to nascent pre-mRNAs was estimated by measuring the relative level of the protein at the transcription site (TS, visualized as a nuclear dot by in situ hybridization with a MS2-Cy3 probe) compared with its level at a neighboring NS ( Figure 11A and Figure S3).…”

“…HeLa cells (ATCC, Manassas, VA), U 2 OS-tTA (Theis-Febvre et al, 2003), 2E11 cell line (Boireau et al, 2007;du Chéné et al, 2007), and MelJuso cell line expressing constitutively the LMP2-GFP fusion protein (Reits et al, 1997) were cultured as described in the respective articles. U 2 OS-tTA cells expressing stably ␣7-CFP or CFP were established as described (Theis-Febvre et al, 2003).…”