Institute of Advanced Virology, GVN Affiliate
Trivandrum, Kerala, India
What are you and your institution currently working on regarding COVID-19
I am the Director at Institute of Advanced Virology, Trivandrum, Kerala, India.
This institute focuses on studying viruses causing infectious diseases in humans, such as SARS-CoV-2, HIV, dengue, influenza, hepatitis, and other viruses. We will be carrying out basic research in the areas of diagnostics, epidemiology, and pathogenesis and will establish a world class infrastructure to address emerging and re-emerging viral diseases. We wish to actively collaborate with all GVN members on translational research to provide interventional strategies to fight these human viruses. Training and education will be vital components of this institute, as we have to generate the next generation of virologists who can provide innovative strategies for fighting existing and emerging pathogens.
We (lead author Dr Ritu Mishra) showed that the SARS-CoV-2 spike protein itself is sufficient to modify exosomal cargo that affects the central nervous system. Micro-RNAs 148a and 590 get internalized by microglia, and USP33/IRF9 axis is impacted. Our studies demonstrate that modified exosomes regulate major pro-inflammatory cytokines, thus triggering neuroinflammation. This paper has been accepted in Frontiers in Immunology (Viral Immunology section). We wish to correlate this finding to clinical outcome of COVID-19 patients.
Summary of Research
Humans and pathogens (viruses/bacteria) have co-evolved during evolution. The pathogens are known to modulate host cell machinery in a manner that ensures their existence. Host cells on the other hand, mount an antiviral or antibacterial response in the form of devising host restriction factors. Indeed, in case of HIV-1, a number of host restriction factors (Tetherin, APOBEC, etc) have been identified. Viruses, however, have devised many mechanisms to overcome these restriction factors and HIV-1 accessory proteins are particularly adept at doing so. HIV-1 is known to modulate levels of key cellular regulators (p53 or components of innate immunity) of homeostasis with significant implications for replication fitness and pathogenesis.
HIV-1 accessory and regulatory genes (Tat, Rev, Nef, Vpu, Vpr) are multifunctional and govern pathogenesis by modulating p53, via set of miRNAs, exploiting cellular ubiquitination machinery or by their ability to suppress siRNA mediated functions or by multiple other mechanisms, notably being B-TrcP mediated functions of Vpu. The functional relevance of such perturbations is key to understanding HIV-1 pathogenesis. The various genetic subtypes, the extent of genetic variants and their functional implications among North-Indian individuals infected with HIV-1 genes or the characterization of host genes that are known to be associated with progression of the disease or the lack of it, are of fundamental importance for gaining insights into HIV-1 pathogenesis and devising novel ways (small molecules, siRNAs, miRNAs etc) to interfere with its replication and progression. Mechanisms responsible for apoptosis, ubiquitination and autophagy and their cross-talk seem to play an important role in HIV pathogenesis and needs to be studied in detail to gain insight about a remarkably successful virus, such as HIV.
About the Institute
The Institute of Advanced Virology established in 2019 in the Bio 360 Life Sciences Park, Thonnakkal, Trivandrum by the Government of Kerala is envisioned as an institute of global standards, networking Global Virology Institutes with most modern laboratories, focusing on research, diagnosis, and management of emerging and re-emerging infectious viral diseases. It will be a centre of excellence working in collaboration with international institutions for training and education in the context of research, covering basic science and translational research, providing sufficient scientific inputs to enable the prevention and control of viral infections.
The Institute shall have all infrastructure and human resources required to carry out high end research needed to study the virus and viral infections in a multifarious approach. The Institute will strengthen epidemic preparedness, rapid response and risk communication to the public apart from the high-end research in the area of basic as well as translational virology. The Institute shall have the bio-safety level measures to handle high-risk viruses (Bio-safety Level 3 initially and eventually to Level 4).
The campus at Thonnakkal, Thiruvananthapuram, has two phases, Phase I and Phase II consisting of Phase IA Prefab building (25,000 sq. ft.) of 2 floors housing Administrative block, Bio labs, Common Instrumentation room, Bio-safety level facilities and Diagnostic facilities and Phase IB main building (78,000 sq. ft.) of 3 floors with Administrative block, Bio labs, Bio safety level facilities and functional division.
The key ingredients for the future development is to attract talented young scientists to join the research team; to nurture healthy and stimulating scientific environment; to encourage friendly competition, fruitful collaborations and free discussions; to take full advantage of scientific exchange and cooperation with both national and international scientists, especially in the emerging interdisciplinary areas.
The Institute is envisaged to become a center of excellence in research in advanced virology research, to act as a platform for productive scientific exchange at the most advanced international level, to build up a basis for fostering and bringing up young talents, so as to play a crucial role in addressing local, national and global needs in virology research and make important contributions to science in the world scale.