Back to Search Start Over

In vitroreactivation of latent HIV-1 by cytostatic bis(thiosemicarbazonate) gold(III) complexes

In vitroreactivation of latent HIV-1 by cytostatic bis(thiosemicarbazonate) gold(III) complexes

Authors :
Pascaline Nanga Fonteh
Debra Meyer
Source :
BMC Infectious Diseases
Publication Year :
2014
Publisher :
Springer Science and Business Media LLC, 2014.

Abstract

Background A number of cytostatic agents have been investigated for the ability to reactivate latent viral reservoirs, which is a major prerequisite for the eradication of HIV-1 infection. Two cytostatic bis(thiosemicarbazonate) gold(III) complexes (designated 1 and 2) were tested for this potential in the U1 latency model of HIV-1 infection. Methods Cell viability in the presence or absence of 1 and 2 was determined using a tetrazolium dye and evidence of reactivation was assessed by p24 antigen capture following exposure to a latency stimulant, phorbol myristate acetate (PMA) and or test compounds. The latency reactivation mechanism was explored by determining the effect of the complexes on protein kinase C (PKC), histone deacetylases (HDAC) and proinflammatory cytokine production. Results The CC50 of the complexes in U1 cells were 0.53 ± 0.12 μM for 1 and 1.0 ± 0.4 μM for 2. In the absence of PMA and at non toxic concentrations of 0.2 and 0.5 μM, 1 and 2 significantly (p ≤ 0.02) reactivated virus in U1 cells by 2.7 and 2.3 fold respectively. In comparison, a 2.6 fold increase (p = 0.03) in viral reactivation was observed for hydroxyurea (HU), which was used as a cytostatic and latent HIV reactivation control. Viral reactivation was absent for the complexes during co-stimulation with PMA indicating the lack of an additive effect between the chemicals as well as an absence of inhibition of PMA induced HIV reactivation but for HU inhibition of the stimulant’s activity was observed (p = 0.01). Complex 1 and 2 activated PKC activity by up to 32% (p

Details

ISSN :
14712334
Volume :
14
Database :
OpenAIRE
Journal :
BMC Infectious Diseases
Accession number :
edsair.doi.dedup.....ca58401086d19b2282798019cad8f1bc
Full Text :
https://doi.org/10.1186/s12879-014-0680-3