The focus of my laboratory is the host response to human RNA viral infections such as Dengue and Coronavirus. RIG-I like receptor (RLR) pathway is a major innate immune response pathway in mammals, that recognizes double stranded RNA intermediates of replication in RNA viruses. Activation of type-I interferons (IFN) is the outcome of such response that is mediated through a key mitochondrial membrane-associated protein, MAVS. Beyond the sketches of these responses, deeper details of these regulations in various cell types are still missing. In one of our recent findings, we identified that epithelial-mesenchymal transition (EMT) is caused by a broad range of viruses and EMT-TFs are activated as part of RLR signalling that promotes antiviral state in a strong way. Various viral proteins are known to interfere with IFN signalling, neutralizing the pathway at multiple nodes. Our laboratory has been studying the delayed response of RLR pathway following SARS-CoV-2 infection in epithelial cells using infectious SARS-CoV-2 particles. Of particular interest is understanding the molecular mechanisms by which some of the recently evolved variants of the virus, such as Alpha- and Delta are able to replicate by evading the host innate immune system. Since host factors are key to the success of viral infection, their differential manipulation by distinct variants is an important aspect in these studies.

Selected Publications

George, A., Panda, S., Kudmulwar, D., Chhatbar, S.D., Nayak, S. C and Krishnan, H.H. 2012. Hepatitis C virus NS5A binds to the mRNA Cap binding eIF4F complex and upregulates host translation initiation machinery through 4EBP1 inactivation. J. Biol. Chemistry. 10; 287(7): 5042-58.

Vedagiri, D., Gupta, D., Mishra, A., Krishna, G., Bhaskar, M., Basu, A., Nayak, D., Kalia, M., Veettil, M.V., and Harshan, K.H. Retinoic acid Inducible Gene-I like Receptors Activate Snail and Slug to Limit RNA Viral Infections. J. Virology, Vol. 95, No. 21. October 2021. https://doi.org/10.1128/JVI.01216-21.

Gupta, D., Parthasarathy, H., Tandel, D., Sah, V., Vedagiri, D., and Harshan, K.H. Inactivation of SARS-CoV-2 by ?-propiolactone Causes Aggregation of Viral Particles and Loss of Antigenic Potential. Virus Research. 305. 2021, 198555. https://doi.org/10.1016/j.virusres.2021.198555.

Gupta, D., Ahmed, F., Tandel, D., Parthasarathy, H., Vedagiri, D., Sah, V., Mohan, K B, Daga, S., Khan, R A., Kondiparthi, C., Savari, P., Jain, S., Daga, J., Reddy, S., Kumar, J M., Khan, N., and Harshan, K.H. Equine immunoglobulin fragment F(ab’)2 displays high neutralizing capability against multiple SARS-CoV-2 variants. Clinical Immunology. 237 (2022) 108981. https://doi.org/10.1016/j.clim.2022.108981.

Tandel, D., Sah, V., Singh, N K., Potharaju, P S., Gupta, D., Shrivastava, S., Sowpati, D T and Harshan, K.H. SARS-CoV-2 Variant Delta Potently Suppresses Innate Immune Response and Evades Interferon-Activated Antiviral Responses in Human Colon Epithelial Cells. Microbiology Spectrum. 2022 Sep 8;e0160422. doi: https://doi.org/10.1128/spectrum.01604-22.