Abstract
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.
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Abbreviations
- BN-PAGE:
-
Blue Native poly-acrylamide gel electrophoresis
- PBMC:
-
Peripheral blood mononuclear cells
- STS:
-
Staurosporine
- TNF-α:
-
Tumor necrosis factor-alpha
- ROS:
-
Reactive oxygen species
- MOI:
-
Multiplicity of infection
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Acknowledgments
We are thankful to Dr. G C Mishra, Director, NCCS for his support and constant encouragement. We thank Manish Kumar and Dyavar Ravi for their technical help. We also thank Dr. B. Saha, Dr. Debi Sarkar and Dr. Robin Mukhopadhyaya for critically reading the manuscript. This work was supported by Department of Biotechnology, Govt. of India. MKT and ZA are Senior Research Fellow of Council of Scientific and Industrial Research (CSIR), Govt. of India.
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Tripathy, M.K., Ahmed, Z., Ladha, J.S. et al. The cell death regulator GRIM-19 is involved in HIV-1 induced T-cell apoptosis. Apoptosis 15, 1453–1460 (2010). https://doi.org/10.1007/s10495-010-0527-3
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DOI: https://doi.org/10.1007/s10495-010-0527-3