Life Sciences & Biotechnology
Title : | Identifying the role of host F-box proteins, a component of E3 ubiquitin ligase complex, in HIV-1 pathogenesis and their potential use as therapeutic target against the virus |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Virology |
Principal Investigator : | Dr. Debashis Mitra, National Centre for Cell science, Pune, Maharashtra |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | dmitra01@yahoo.co.in |
Details
Executive Summary : | HIV-1 utilizes host cell UPs for infection, replication as well as in maturation. HIV-1 infects CD4+ T cells and then virus destroys the cell-surface protein CD4. HIV-1 utilizes Vpu to facilitate degradation of CD4 through proteasome with the help of E3 enzyme (Magadan JG et al PLos Pathogens 2010, 6, e1000869). similarly, HIV-1 modulates the function of sAMHD1, cyclin T, cyclin L2 during host cell cycle progression to facilitate pathogenesis (Rice AP et al Cell Host & Microbe 17, June 10, 2015; Hrecka K et al Nature 474, 658-661; Laguette N. et al Nature 474, 654-657). HIV-1 manipulates host cell cycle progression for their own nefarious purposes by utilizing the UPs system. HIV-1 encoded proteins Vif accelerates the transition from G1 to s phase as well as arrest the cells at the G2 and M phase of the cell cycle through modulating the host cell UPs (Wang J et al Blood 2011 117(4): 1260-1269). E3 ubiquitin ligases are the important players in UPs system. They facilitate the ubiquitination of proteins. Though previous studies highlight the importance of ubiquitin proteasome system of the host in HIV-1 pathogenesis; however, the importance of E3 ubiquitin ligases specifically in HIV-1 pathogenesis remains to be clearly elucidated. Cell cycle progression is precisely controlled by ubiquitin proteasome system. Recent studies showed that RING finger ubiquitin ligases of ubiquitin proteasome system play crucial role in cell cycle progression and cellular signaling. We therefore anticipate that RING finger ubiquitin ligases of the host may play important role in HIV-1 pathogenesis. In the proposed study, we aim to identify the RING finger ubiquitin ligases involved in HIV-1 infection and replication and in so doing identify potential targets for therapy. |
Co-PI: | Dr. Manas Kumar santra, National Centre for Cell science, Pune, Maharashtra |
Total Budget (INR): | 62,57,880 |
Organizations involved