Exploitation of cellular machinery by HIV-1

HIV-1 is notorious in accumulating a great deal of variations in several of its regulatory and accessory genes. Some of HIV-1 genetic subtype C from India shows a B/C recombinant structure with remarkable 3 or 4 NFkB sites in promoter. Most of Vpr genes of Indian isolates show L64P mutation, a helix breaker, which abrogates its ability to inhibit whole cell ubiquitination. Tat was earlier reported to be an RNAi-suppressor. We show that, another regulatory protein REV is an equally potent RNAi-suppressor and that Arginine rich motif is critically important (also important in case of Dengue virus). HIV-1 exploits the biosynthetic machinery by modulating the mTORC1 levels and that Tat alone is sufficient for this activity. Intracellular stability of various proteins of HIV-1 is critically important. Rev regulates the level of Tat indirectly via NQO1. HIV-1 also exploits MDM2 to enhance its replication. Vpu stabilizes p53 via B-TrCP which increases apoptosis in human T-cells. Stability of Vif and Tat is governed by CHIP (an E3 ligase). Intracellular stability is governed by ubiquitination and de-ubiquitination. We show that USP7 Deubiquitinase (DUB), controls the stability of HIV-1 Tat protein.  Micro-RNA- 34a upregulates HIV-1 replication by targeting a phospotase, PNUTS. Thus, HIV-1 proteins are ploy-functional and dissecting out the ultimate role in infection continues to remain a challenge in the absence of an optimal animal model.

About the Speaker:

Akhil C. Banerjea obtained his Ph.D. from National Institute of Virology, University of Pune. He was a Post Doctorate Fellow and Faculty at Duke University Medical Center, North-Carolina, USA and Senior Staff-Fellow at National Institutes of Health, Maryland, USA. He has published more than 110 papers in international peer reviewed journals and contributed 14 invited chapters/ reviews. He has guided 12 PhD students.  He is the recipient of National Awards of ICMR (1982), National Foreign-Associateship award of DBT (1998), National Bio-Science Award for Career Development of DB (2001), SR Scientist Indian Immunology Society Oration Award (2012) and Ranbaxy award for medical research (2014). He is a Member-Editorial Board of several International Journals. He is a member of the several task forces of DBT and ICMR. He is a member of the National Academy of Sciences and Fellow of the Indian National Science Academy (INSA).