Immunoneuropathogenesis of HIV-1 clades B and C: role of redox expression and thiol modification.
Immunoneuropathogenesis of HIV-1 clades B and C: role of redox expression and thiol modification.
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DOI:
10.1016/j.freeradbiomed.2013.12.025
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发表时间:
2014-04
影响因子:
7.4
通讯作者:
Nair, Madhavan P. N.
中科院分区:
文献类型:
--
作者:
Samikkannu, Thangavel;Rao, Kurapati V. K.;Kanthikeel, Sudhessh Pilakka;Atluri, Venkata Subba Rao;Agudelo, Marisela;Roy, Upal;Nair, Madhavan P. N.
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.
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DOI:
10.1073/pnas.90.16.7632
发表时间:
1993-08-15
影响因子:
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