A histone deacetylase network regulates epigenetic reprogramming and viral silencing in HIV-infected cells.
Cell Chem Biol
; 30(12): 1617-1633.e9, 2023 12 21.
Article
em En
| MEDLINE
| ID: mdl-38134881
ABSTRACT
A long-lived latent reservoir of HIV-1-infected CD4 T cells persists with antiretroviral therapy and prevents cure. We report that the emergence of latently infected primary CD4 T cells requires the activity of histone deacetylase enzymes HDAC1/2 and HDAC3. Data from targeted HDAC molecules, an HDAC3-directed PROTAC, and CRISPR-Cas9 knockout experiments converge on a model where either HDAC1/2 or HDAC3 targeting can prevent latency, whereas all three enzymes must be targeted to achieve latency reversal. Furthermore, HDACi treatment targets features of memory T cells that are linked to proviral latency and persistence. Latency prevention is associated with increased H3K9ac at the proviral LTR promoter region and decreased H3K9me3, suggesting that this epigenetic switch is a key proviral silencing mechanism that depends on HDAC activity. These findings support further mechanistic work on latency initiation and eventual clinical studies of HDAC inhibitors to interfere with latency initiation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Histona Desacetilases
Limite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos