Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage.
Gene Expression Regulation, Viral
HEK293 Cells
HIV Infections
/ genetics
HIV-1
/ genetics
Humans
Myeloid Cells
/ metabolism
Repressor Proteins
/ genetics
Transcription, Genetic
Tripartite Motif-Containing Protein 28
/ genetics
Tumor Suppressor Proteins
/ genetics
tat Gene Products, Human Immunodeficiency Virus
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 01 2021
29 01 2021
Historique:
received:
05
06
2020
accepted:
13
01
2021
entrez:
30
1
2021
pubmed:
31
1
2021
medline:
16
11
2021
Statut:
epublish
Résumé
HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP1 is known as a potent repressor of gene transcription. Here we report that KAP1 represses HIV-1 gene expression in myeloid cells including microglial cells, the major reservoir of the central nervous system. Mechanistically, KAP1 interacts and colocalizes with the viral transactivator Tat to promote its degradation via the proteasome pathway and repress HIV-1 gene expression. In myeloid models of latent HIV-1 infection, the depletion of KAP1 increased viral gene elongation and reactivated HIV-1 expression. Bound to the latent HIV-1 promoter, KAP1 associates and cooperates with CTIP2, a key epigenetic silencer of HIV-1 expression in microglial cells. In addition, Tat and CTIP2 compete for KAP1 binding suggesting a dynamic modulation of the KAP1 cellular partners upon HIV-1 infection. Altogether, our results suggest that KAP1 contributes to the establishment and the persistence of HIV-1 latency in myeloid cells.
Identifiants
pubmed: 33514850
doi: 10.1038/s41598-021-82164-w
pii: 10.1038/s41598-021-82164-w
pmc: PMC7846785
doi:
Substances chimiques
BCL11B protein, human
0
Repressor Proteins
0
Tumor Suppressor Proteins
0
tat Gene Products, Human Immunodeficiency Virus
0
TRIM28 protein, human
EC 2.3.2.27
Tripartite Motif-Containing Protein 28
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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