Immunoneuropathogenesis of HIV-1 clades B and C: role of redox expression and thiol modification. Academic Article uri icon


  • Previous studies have shown that, during infection, HIV-1 clade B and clade C differentially contribute to the neuropathogenesis and development of HIV-associated neurocognitive disorders (HANDs). The low-molecular-weight tripeptide glutathione (GSH) alters the redox balance and leads to the generation of reactive oxygen species, which play a significant role in the neuropathogenesis of HANDs. We hypothesized that the HIV-1 clade B and clade C viruses and their respective Tat proteins exert differential effects on monocyte-derived immature dendritic cells (IDCs) and neuroblastoma cells (SK-N-MC) by redox activation, which leads to immunoneuropathogenesis. 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 IDCs 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 and reduced the GSH/GSSG ratio and subsequent downregulation of gene expression and protein modification of GSS, GPx1, SOD1, and CAT compared to infection with the clade C virus or treatment with the clade C Tat protein. Thus, our studies demonstrate that HIV-1 clades B and C exert differential effects of redox expression and thiol modification. HIV-1 clade B potentially induces oxidative stress, leading to more immunoneuropathogenesis than infection with HIV-1 clade C.

published proceedings

  • Free Radic Biol Med

altmetric score

  • 1.25

author list (cited authors)

  • Samikkannu, T., Rao, K., Kanthikeel, S. P., Atluri, V., Agudelo, M., Roy, U., & Nair, M.

citation count

  • 17

complete list of authors

  • Samikkannu, Thangavel||Rao, Kurapati VK||Kanthikeel, Sudhessh Pilakka||Atluri, Venkata Subba Rao||Agudelo, Marisela||Roy, Upal||Nair, Madhavan PN

publication date

  • January 2014