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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
- 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
- Subjects :
- Thiosemicarbazones
Anti-HIV Agents
Latent virus reactivation
HIV Infections
In Vitro Techniques
Biology
Virus
Cell Line
Proinflammatory cytokine
Coordination Complexes
Protein kinase C
Virus latency
medicine
Humans
Viability assay
HIV eradication
medicine.disease
Virology
Molecular biology
In vitro
Virus Latency
Infectious Diseases
Bis(thiosemicarbazonate) gold(III) complexes
Cell culture
TNF-α
HIV-1
Virus Activation
Tumor necrosis factor alpha
Gold
Research Article
Subjects
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