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http://hdl.handle.net/10603/428856
Title: | Role of Hydrogen Sulfide Gas in Modulating HIV 1 Latency and Reactivation |
Researcher: | Pal, Virender Kumar |
Guide(s): | Singh, Amit |
Keywords: | Genetics and Heredity Life Sciences Molecular Biology and Genetics |
University: | Indian Institute of Science Bangalore |
Completed Date: | 2021 |
Abstract: | Human Immunodeficiency Virus 1 (HIV-1) remains a global public health threat, claiming 690 thousand people s lives in 2020 and causing 1.5 million new infections. The advent of combinatorial antiretroviral therapy (ART) have curbed the spread of the HIV-1 epidemic by limiting new infections rate. However, ART is not a curative therapy, and HIV-1 persists in latent reservoirs mainly comprising long-lived memory CD4+ T cells. Notably, low ART treatment coverage and cases of poor therapy adherence lead to replenishment of latent reservoirs and the emergence of drug-resistant variants. Thus, to eradicate HIV-1, it is important to understand how the virus establishes latency, maintains stable cellular reservoirs, and promotes rebound upon interruption of antiretroviral therapy (ART). Cellular redox status has been observed as a key determinant modulating HIV-1 latency and reactivation. HIV-1 patients display the hallmark of oxidative stress with reduced levels of major cellular antioxidants, glutathione (GSH), and thioredoxin (Trx) systems. The current approach to target latent HIV-1 includes a shock and kill approach, which utilizes latency reversing agents (LRAs) to reactivate HIV-1 and kill infected cells by immune-based mechanisms [Chapter 1]. The LRAs belonging to histone deacetylase inhibitors class, when used in combination with GSH biosynthesis inhibitor, BSO, induce robust oxidative stress and heightened HIV-1 reactivation. In this direction, the use of antioxidant molecules, e.g., N-acetyl cysteine (NAC), has been shown to limit HIV-1 reactivation, but the molecular mechanism involved in NAC action remains understudied. Recently, NAC has been shown to exert its effect by inducing the biogenesis of a novel antioxidant gasotransmitter molecule, hydrogen sulfide (H2S). Previously considered as a toxic gas, but literature in the past two decades suggests the cytoprotective and antioxidant role of H2S in several patho-physiological conditions. In this study,... |
Pagination: | vii, 154 |
URI: | http://hdl.handle.net/10603/428856 |
Appears in Departments: | Microbiology and Cell Biology |
Files in This Item:
File | Description | Size | Format | |
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01_title.pdf | Attached File | 319.78 kB | Adobe PDF | View/Open |
02_prelim pages.pdf | 1.15 MB | Adobe PDF | View/Open | |
03_table of contents.pdf | 189.59 kB | Adobe PDF | View/Open | |
04_abstract.pdf | 218.1 kB | Adobe PDF | View/Open | |
05_chapter 1.pdf | 5.8 MB | Adobe PDF | View/Open | |
06_chapter 2.pdf | 8.52 MB | Adobe PDF | View/Open | |
07_chapter 3.pdf | 3.12 MB | Adobe PDF | View/Open | |
08_chapter 4.pdf | 2.99 MB | Adobe PDF | View/Open | |
11_annexure.pdf | 3.07 MB | Adobe PDF | View/Open | |
80_recommendation.pdf | 990.32 kB | Adobe PDF | View/Open |
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