Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294
Braz. j. infect. dis
;
24(2): 150-159, Mar.-Apr. 2020. tab, graf
Artículo
en Inglés
| LILACS, ColecionaSUS
| ID: biblio-1132431
ABSTRACT
ABSTRACT Background:
Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals.Results:
NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4).Conclusion:
NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Quinazolinas
/
Azepinas
/
Activación Viral
/
Infecciones por VIH
/
VIH-1
/
Niacinamida
/
Metiltransferasas
Tipo de estudio:
Factores de riesgo
Límite:
Adulto
/
Femenino
/
Humanos
/
Masculino
Idioma:
Inglés
Revista:
Braz. j. infect. dis
Año:
2020
Tipo del documento:
Artículo
/
Documento de proyecto
Institución/País de afiliación:
Emory University/GE
/
Federal University of Sao Paulo/BR
/
Federal University of São Paulo/BR
/
Institute of Adolfo Lutz/BR
/
Northwestern University/US
/
Wistar Institute/US
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