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
Article
de En
| LILACS, ColecionaSUS
| ID: biblio-1132431
Bibliothèque responsable:
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.Mots clés
Texte intégral:
1
Indice:
LILACS
Sujet Principal:
Quinazolines
/
Azépines
/
Activation virale
/
Infections à VIH
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VIH-1 (Virus de l'Immunodéficience Humaine de type 1)
/
Nicotinamide
/
Methyltransferases
Type d'étude:
Risk_factors_studies
Limites du sujet:
Adult
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Female
/
Humans
/
Male
langue:
En
Texte intégral:
Braz. j. infect. dis
Thème du journal:
DOENCAS TRANSMISSIVEIS
Année:
2020
Type:
Article
/
Project document