Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency.
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, HP1gamma and histone H3Lys9 trimethylation play a major role in chromatin-mediated repression of integrated HIV-1 gene expression. Suv39H1, HP1gamma 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 HP1gamma RNA interference.
du Chéné
Isaure
I
Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, UPR 1142, Montpellier, France.
Basyuk
Euguenia
E
Lin
Yea-Lih
YL
Triboulet
Robinson
R
Knezevich
Anna
A
Chable-Bessia
Christine
C
Mettling
Clement
C
Baillat
Vincent
V
Reynes
Jacques
J
Corbeau
Pierre
P
Bertrand
Edouard
E
Marcello
Alessandro
A
Emiliani
Stephane
S
Kiernan
Rosemary
R
Benkirane
Monsef
M
D018797:Cell Cycle Proteins / Q000502:physiology; D002478:Cells, Cultured; D002843:Chromatin / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D020868:Gene Silencing; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000502:physiology; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008780:Methyltransferases / Q000502:physiology*; D008954:Models, Biological; D042925:Positive Transcriptional Elongation Factor B / Q000502:physiology; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016662:Virus Integration; D017735:Virus Latency; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D051548:Histone Acetyltransferases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D008780:Methyltransferases; D042925:Positive Transcriptional Elongation Factor B; D011496:Protein Methyltransferases; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C518294:CBX3 protein, human; C407843:SUV39H1 protein, human