Viruses are among the most successful pathogens that co-existed with the hosts by maintaining a precarious balance between the two for their successful existence. Being predatory in nature, viruses are constantly in the pursuit of survival, and thus, there exists a constant struggle for endurance between the viruses and their hosts: viruses pursue the host for their propagation, and the hosts, on the other hand, defy the viral intrusions owing to their well-developed and interconnected network of innate and adaptive immune defense mechanisms. Our laboratory focuses on these assiduous struggles between viruses and the immune system, in particular between viruses and the complement system.

In particular, our laboratory has shown that the RCA homolog encoded by Kaposi’s sarcoma-associated herpesvirus (named Kaposica) inhibits complement. In addition, we and others have also shown that RCA homologs encoded by KSHV and other viruses (vaccinia virus, variola virus, and Herpesvirus saimiri) inhibit complement by targeting the C3-convertases. Our group has also contributed to mapping the functional domains, determinants, and species specificity of these viral proteins. Our studies revealed that the ‘functional blocks’ required for regulatory activities of the viral regulators are conserved in the human regulators as well. Currently, studies in our laboratory are directed towards understanding the role of virally encoded complement regulators in viral pathogenesis.

Additionally, we also focus on understanding the role of intact complement as well as individual pathways during viral infections. Our lab showed that synergy between the classical and alternative pathways is critical for providing effective protection against the pandemic influenza A(H1N1)2009 virus infection. Further, our data indicated that complement synthesized by the splenic B cells and anaphylatoxin-mediated signalling plays a major role in providing protection. Currently, our lab is using both in vivo and in vitro approaches to further dissect the immunological basis of protection provided by the complement system against viral infections.

• Wellcome Trust Overseas Senior Fellow in Biomedical Science in India (2001-2006).
• Fellow, National Academy of Sciences, Allahabad, India (2009).
• Fellow, Indian National Science Academy, New Delhi, India (2016).
• Fellow, Indian Academy of Sciences, Bengaluru, India (2019).
• J C Bose National Fellow (2020).

• 1. Lambris, J.D. and Sahu, A. (2001) Peptides which inhibit complement activation. USA patent #6,319,897. The US FDA approved a PEGylated compstatin Empaveli and SYFOVRE for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and geographic atrophy (GA) secondary to age-related macular degeneration (AMD), respectively.
• 2. Sahu, A. and Kadam, A.P. Peptides that inhibit factor B, C2 and complement activation, and their uses. (Application #889/DEL/2010 dated 13.4.2010). Indian Patent #2884803.
• 3. Sahu, A., Ojha, H., Ghosh, P., Barage and Panwar, H.S. (2019) DAF-MCP chimeric protein, process to manufacture the same and use of the chimeric protein for treating pathological conditions involving the complement system. US Application #: PCT/IN2020/050337 filed on April 9, 2020.

1. Shende, R., Wong, S.S.W., Meitei, H.T., Lal, G., Madan, T., Aimanianda, V., Pal J.K., Sahu, A. (2022) Protective role of host complement system in Aspergillus fumigatus infection. Front. Immunol. 13:978152.
2. Ghate, A., Sharma, S., Agrawal, P. and Sahu, A. (2021) Differential expression of complement receptors CR1/2 and CR4 by murine M1 and M2 macrophages. Mol. Immunol., 137: 75-83. PMID: 34229135 DOI: 10.1016/j.molimm.2021.06.003
3. Panwar, H.S., Ojha, H., Ghosh, P., Barage, S.H., Raut, S. and Sahu, A. (2019) Molecular engineering of an efficient four-domain DAF-MCP chimera reveals the presence of functional modularity in RCA proteins, Proc. Natl. Acad. Sci. USA., 116(20): 9953-9958. PMID: 31036650 DOI: 10.1073/pnas.1818573116
4. Ojha, H., Ghosh, P., Panwar, H.S., Shende, R., Gondane, A., Mande, S.C. and Sahu, A. (2019) Spatially conserved motifs in complement control protein domains determine functionality in regulators of complement activation-family proteins, Commun. Biol., 2:290: 1-12. DOI: 10.1038/s42003-019-0529-9
5. Rattan, A., Pawar, S.D., Nawadkar, R., Kulkarni, N., Lal, G., Mullick, J., and Sahu, A. (2017) Synergy between the classical and alternative pathways of complement is essential for conferring effective protection against the pandemic influenza A(H1N1) 2009 virus infection, PLoS Pathog, 13(3): 1-26. PMID: 28301559 DOI: 10.1371/journal.ppat.1006
6. Gautam, A.K., Panse, Y., Reza, J.M., Mullick, J. Ghosh, P., and Sahu, A. (2015) Mutational analysis of Kaposica reveals that bridging of MG2 and CUB domains of target protein is crucial for the cofactor activity of RCA proteins, Proc Natl Acad Sci USA, 112(41): 12794-9. PMID: 26420870 DOI: 10.1073/pnas.1506449112