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
in English
| 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.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Quinazolines
/
Azepines
/
Virus Activation
/
HIV Infections
/
HIV-1
/
Niacinamide
/
Methyltransferases
Type of study:
Risk factors
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
English
Journal:
Braz. j. infect. dis
Year:
2020
Type:
Article
/
Project document
Institution/Affiliation country:
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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