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.
Dubey, S.K., Shrinet, J., Sunil, S. 2019. Aedes aegypti microRNA, miR-2944b-5p interacts with 3’UTR of chikungunya virus and cellular target vps-13 to regulate viral replication. PloS Negl Trop Dis 13 e0007429 PubMed link
Jain, J., Narayanan, V., Kumar, A., Shrinet, J., Srivastava, P., Chaturvedi, S., Sunil, S. 2019, Establishment and comparison of pathogenicity and related neurotropism in two age groups of immune competent mice, C57BL/6J using an Indian isolate of chikungunya virus (CHIKV). Viruses 11 pii: E578 PubMed link
Kumar, A., Priyanshu Srivastava, P., Sirisena, PDNN., Dubey, S.K., Ramesh, K., Shrinet, J., Sunil, S. 2018. Mosquito Innate Immunity. Insects 9, 95 PubMed link
Sirisena, PDNN., Kumar, A., Sunil, S. 2018. Evaluation of Aedes aegypti life table attributes upon chikungunya virus replication reveals impact on egg laying pathways. J Med Entomol doi: 10.1093/jme/tjy097 PubMed link
Shrinet, J., Bhavesh, N.S., Sunil, S. 2018. Understanding Oxidative Stress in Aedes during chikungunya and dengue virus infections using Integromics Analysis. Viruses 10, 314; doi:10.3390. PubMed link
Jain, J., Okabayashi, T., Kaur, N., Nakayama, E., Shioda, T., Gaind, R., Kurosu, T., Sunil, S. 2018. Evaluation of an immunochromatography rapid diagnosis kit for detection of chikungunya virus antigen in India, a dengue-endemic country. Virol J 15, 84 PubMed link