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
; Braz. j. infect. dis;24(2): 150-159, Mar.-Apr. 2020. tab, graf
Article
em En
| LILACS, ColecionaSUS
| ID: biblio-1132431
Biblioteca responsável:
BR1.1
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
/
ColecionaSUS
Assunto principal:
Quinazolinas
/
Azepinas
/
Ativação Viral
/
Infecções por HIV
/
HIV-1
/
Niacinamida
/
Metiltransferases
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Braz. j. infect. dis
Assunto da revista:
DOENCAS TRANSMISSIVEIS
Ano de publicação:
2020
Tipo de documento:
Article
/
Project document
País de afiliação:
Brasil
/
Estados Unidos