Immunoneuropathogenesis of HIV-1 clades B and C: role of redox expression and thiol modification.
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.
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
Thangavel
T
Samikkannu
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
Kurapati V K
KV
Rao
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
Sudhessh Pilakka
SP
Kanthikeel
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
Venkata Subba Rao
VS
Atluri
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
Marisela
M
Agudelo
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
Upal
U
Roy
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA. Electronic address: nairm@fiu.edu.
Madhavan P N
MP
Nair
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013438:Sulfhydryl Compounds; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione
Dendritic cells; Free radicals; Glutathione; HIV-1 clade B; HIV-1 clade C; Neuron; Oxidative stress