INFECTIOUS DISEASES / Virology
Vector-borne diseases, arbovirus, vector biology, chikungunya virus, dengue virus, host pathogen interactions, RNAi, functional genomics.
Description of Research
The current focus in the lab is on understanding chikungunya virus (CHIKV) and dengue virus (DENV) evolution and in studying the dynamics of chikungunya virus /dengue virus (CHIKV/DENV) co-infections in vector and host. With respect to CHIKV evolution, we characterize CHIKV isolated from patients over the years and study the changes in the disease pattern and the molecular characterization over the years. Our studies have paved way to understanding chikungunya disease progression and occurrence of co-infections of CHIKV with DENV in the Indian population. Recently, we identified distinct metabolites in clinical samples of chikungunya and dengue mono and co-infections. We show that distinct pathways are regulated during fever, joint pain and chronic phase of the three conditions of disease presentations.
Using genomic tools, we are identifying vector factors that may play a role on pathogen establishment within the vector with primary interests on the insect microRNA populations. Using next generation sequencing technologies, we have provided important insights to the role of microRNAs in pathogenesis and development. Currently, efforts are been made to bring in another layer of data analysis from global proteomic and metabolomics studies thereby integrating the fields of omics to understand the biology of virus-vector interactions.
We are also studying virus derived virulence factors that could be playing important roles in enabling virus to fight insect immunity. In this regard, we have shown that two non-structural proteins, namely, nsP2 and nsP3 exhibit suppressor RNAi activity in both insect and host. These proteins are the first viral RNAi suppressors to be identified in alphavirus, thereby providing new insights to underlying mechanisms for virulence in alphaviruses. Furthermore, we are also interested in identifying vector host factors that may play a role in CHIKV replication and we are using CRISPR-CAS 9 gene editing technologies for this purpose.
Our lab’s long-term research goal is evaluating the mechanism of co-infection in vector. For this purpose, we have already initiated proof of concept experiments to establish co-infections in lab reared Aedes. We have seen that initial viral load of both the viruses are important in establishing co-infections in the vector. We are currently evaluating the role of super-infections of each of the virus to decipher if either of the viruses exhibit competitive suppression in the vector and further evaluate transmission potential of these viruses in the mosquito salivary glands.
The Group has recently been continuing in their efforts in understanding the molecular evolution of arboviruses in the country (Choudhary et al 2021, TRC consortium 2021). The facility for SARS-CoV-2 antiviral testing has been assigned as one of the nodal centres for antiviral testing for the whole of India by the Department of Biotechnology and Indian Council of Medical Research, and the group has contributed in testing several molecules for their anti-SARS-Cov-2 activity and identifying certain promising therapeutic candidates (Panchariya et al., 2021, Lingwana et al., 2021).
Babu N, Mahilkar S, Jayaram A, Ibemgbo SA, Mathur G, Shetty U, Sudandiradas R, Kumar SP, Singh S, Pani SS, Mudgal PP, Shastri JS, Agarwal S, Ratho PK, Baijayantimala M, Chattopadhyay S, Jagadesh A, Sunil S. A cross-sectional investigation of neutralization potential, inflammatory cytokine response, and viral replication among chikungunya patients during 2016-2021 in India. The Lancet Regional Health – Southeast Asia. https://doi.org/10. 1016/j.lansea.2023. 100269.
Srivastava P, Chaudhary S, Malhotra S, Varma B, Sunil S. Transcriptome analysis of human macrophages upon chikungunya virus (CHIKV) infection reveals regulation of distinct signaling and metabolic pathways during early and late stages of infection. 2023. Heliyon. Jun 20;9(6):e17158. doi: 10.1016/j.heliyon.2023.e17158. (IF:3.776)
Kumar R, Mehta D, Nayak D, Sunil S. Characterization of an Aedes ADP ribosylation protein domain and role of post-translational modification during chikungunya virus infection. 2023. Pathogens. May 16;12(5):718. doi: 10.3390/pathogens12050718. (IF: 4.531).
Kumar A, Shrinet J, Sunil S*. Chikungunya virus infection in Aedes aegypti is modulated by L-cysteine, taurine, hypotaurine and glutathione metabolism. 2023. PloS Negl Trop Diseases. May 2;17(5):e0011280. doi: 10.1371/journal.pntd.0011280. eCollection 2023 May.(IF: 4.781)
Yadav K, Rana VS, Anjali, Saurav GK, Rawat N, Kumar A, Sunil S, Singh OP, Rajagopal R. Mucin protein of Aedes aegypti interacts to dengue virus-2 and influences viral infection. 2023. Microbiology Spectrum. Feb 27;11(2):e0250322. doi: 10.1128/spectrum.02503-22. (IF: 9.043)
Kumar R, Mehta D, Chaudhary S, Nayak D, Sunil S*. Impact of CHIKV replication on the global proteome of Aedes albopictus cells. 2022. Proteomes. 10 (4), 38. https://doi.org/10.3390/proteomes10040038