The cell death regulator GRIM-19 is involved in HIV-1 induced T-cell apoptosis.
One of the hallmarks of Human Immunodeficiency Virus-1 (HIV-1) infection is progressive depletion of the infected and bystander CD4+ T-cells by apoptosis. Different mitochondrial proteins have been implicated in this apoptotic process; however, the role of different subunits of mitochondrial oxidative phosphorylation (OXPHOS) complexes in apoptosis is not clearly understood. Some of the OXPHOS complex subunits seem to perform other functions in addition to their primary role in energy generating process. GRIM-19 (gene associated with retinoid-interferon-induced-mortality-19), a subunit of mitochondrial complex-I was previously implicated in Interferon-β and retionoic acid induced apoptosis in many tumor cells. In this study we report, using differential gene expression analysis, that GRIM-19 is up-regulated in HIV-1 infected apoptotic T-cells. A temporal up regulation of this subunit was observed in different HIV-1 infected T-cell lines and human PBMC and the extent of increase correlated to increasing apoptosis and virus production. Moreover, silencing GRIM-19 in HIV-1 infected cells reduced apoptosis, indicating its involvement in HIV-1 induced T-cell death.
Tripathy
Manoj Kumar
MK
National Centre for Cell Science, Ganeshkhind, Pune 411007, India.
Ahmed
Zulfazal
Z
Ladha
Jayashree Sashikant
JS
Mitra
Debashis
D
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics* / Q000276:immunology; D020868:Gene Silencing; D015658:HIV Infections / Q000201:enzymology* / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000821:virology*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010085:Oxidative Phosphorylation; D019311:Staurosporine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D014409:Tumor Necrosis Factor-alpha; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human; D042967:Electron Transport Complex I; D019311:Staurosporine