Immuno-Neuropathogenesis of HIV-1 Clade B and C: Role of Redox Expression and Thiol Modification

• Published in: Free radical biology & medicine Vol. 69; pp. 136 - 144
• Main Authors: Samikkannu, Thangavel, Rao, Kurapati V.K., Kanthikeel, Sudhessh Pilakka, Atluri, Venkata Subba Rao, Agudelo, Marisela, Roy, Upal, Nair, Madhavan P.N.
• Format: Journal Article
• Language: English
• Published: 27-01-2014
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2013.12.025

Previous studies have shown that infection with HIV-1 clade B and clade C differentially contributes to the neuropathogenesis and development of HIV-associated neurocognitive disorders (HAND). The low molecular weight tripeptide glutathione (GSH) alters the redox balance and leads to the generation of reactive oxygen species (ROS), which play a significant role in the neuropathogenesis of HAND. We hypothesized that the HIV-1 clade B and clade C viruses and the respective Tat proteins exert differential effects on monocyte (MC)-derived immature dendritic cells (IDC) and neuroblastoma cells (SK-N-MC) by redox activation, which leads to immuno-neuropathogenesis. The GSH/GSSG ratio and mRNA expression levels and protein modification of glutathione synthetase (GSS), glutathione peroxidase 1 (GPx1), superoxide dismutase 1 (SOD1) and catalase (CAT) were analyzed in IDC infected with HIV-1 clade B or clade C as well as in cells treated with the respective Tat proteins. The results indicated that HIV-1 clade B virus and its Tat protein significantly increased the production of reactive oxygen species (ROS) and reduced the GSH/GSSG ratio and subsequent down-regulation of gene expression and protein modification of GSS, GPx1, SOD1 and CAT than infection with the clade C virus or treatment with the clade C Tat protein. Thus, our studies demonstrate that HIV-1 clade B and C exert differential effects of redox expression and thiol modification. HIV-1 clade B potentially induces oxidative stress, leading to more immuno-neuropathogenesis than infection with HIV-1 clade C.