The Doctor of Philosophy Seminar and Examination of Pallavi Rai

Biography

I earned my DVM degree from G.B. Pant University in 2008 and my diploma in management from MANAGE, Hyderabad in 2009. I have been passionate about working with the rural people and was blessed to interact with them very closely through my various roles in the banking sector, where I worked for 10 years. I joined the Weger-Lucarelli lab in 2019 as an MS student and switched to a PhD in 2020. My research projects focused mainly on studying obesity’s impact on viral pathogenesis and transmission specifically focused on coronaviruses and alphaviruses. During my spare time, I like to cook and spend time with my husband and kids.

Funded by

• National Science Foundation
• Virginia-Maryland College of Veterinary Medicine Office of Research and Graduate Studies

Awards and Academic Achievements

• Outstanding Doctoral Student Award, Virginia Maryland College of Veterinary Medicine, 2023-2024
• Graduate School Doctoral Assistantship, 2023-2024
• Vice-Chancellor’s Silver Medal, 2018
• Alembic Student of the Year, 2018

Lay Language Abstract 

Obesity is a global epidemic associated with chronic systemic inflammation and has been identified as an independent risk factor following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The impact of obesity on COVID-19 severity is based mostly on epidemiological data or research with non-natural hosts of SARS-CoV-2. Therefore, natural models of obesity are required to study the host’s response to coronaviruses. Here we used mouse models of diet-induced obesity and infected them with a mouse coronavirus to account for the host’s natural immune response against the virus. We showed that obesity worsens disease outcome and we also found various genes associated with disease severity in obese mice that correspond to the gene expression patterns in severe COVID-19 patients.

Obesity also worsens the disease outcome following infection with mosquito-borne alphaviruses like chikungunya (CHIKV) and Mayaro (MAYV), however, its impact on the vector’s transmission potential is poorly understood. Using a natural transmission cycle between lean and obese mice and mosquitoes, we showed that obesity reduced alphavirus transmission by mosquitoes. We also found activation of the Toll pathway and downregulation of a gene, tetratricopeptide repeat protein (TTRP), in mosquito midguts exposed to alphavirus-infected obese bloodmeal compared to the lean ones. We further showed that the knockdown of the Toll pathway and TTRP respectively led to increased and reduced infection rates in mosquitoes exposed to various alphaviruses. We also established insulin as a potential antiviral factor in obese bloodmeal.

Publications

In preparation:

• Rai P, Webb EM, Paulson SL, Kang Lin, Lucarelli JW. Determining the impact of obese bloodmeal on alphavirus transmission and mosquito immune response to identify potentially antiviral genes.

Peer reviewed:

• Rai P, Marano JM, Kang L, Coutermarsh-Ott S, Daamen A, Lipsky PE, Lucarelli JW. Obesity fosters severe disease outcomes in a mouse model of coronavirus infection associated with transcriptomic abnormalities. Journal of Medical Virology. 2024 Apr. DOI: 10.1002/jmv.29587.
• Rai P, Webb EM, Lucarelli JW. Insulin reduces the transmission potential of chikungunya virus and activates the Toll pathway in Aedes aegypti mosquitoes. Insect Molecular Biology. 2023 June. DOI:10.1111/imb.12863.
• Rai P, Chuong C, Lucarelli JW. Adenovirus transduction to express human ACE2 causes obesity-specific morbidity in mice, impeding studies on the effect of host nutritional status on SARS-CoV-2 pathogenesis. Virology. 2021 Nov. DOI: 10.1016/j.virol.2021.08.014
• Chuong C, Cereghino CN, Rai P, Lucarelli JW. Enhanced attenuation of chikungunya vaccines expressing antiviral cytokines. Npj Vaccines. 2024 Mar. DOI: 10.1038/s41541-024-00843-x.
• Muddassar H, Rai P, Melissa M, Lucarelli JW. Optimized protocol for mouse footpad immune cell isolation for single-cell RNA sequencing and flow cytometry. STAR protocols. 2023 July. DOI: 10.1016/j.xpro.2023.102409.
• Webb EM, Compton A, Rai P, Chuong C, Paulson SL, Lucarelli JW. Expression of anti-chikungunya single-domain antibodies in transgenic Aedes aegypti reduces vector competence for chikungunya virus and Mayaro virus. Frontiers Microbiology. 2023 June. DOI: 10.3389/fmicb.2023.1189176.
• Cereghino C, Roesch F, Carrau L, Hardy A, Marano JM, Bates TA, Rai P, Lucarelli JW. The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito. PLOS Pathogens. 2023 April. DOI:10.1371/journal.ppat.1010491.
• Chuong C, DuChane CM, Webb EM, Rai P, Marano JM, Bernier CM, Merola JS, Weger-Lucarelli J. Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2. Viruses. 2021 May. DOI: 10.3390/v13060980. 
• Bates TA, Chuong C, Rai P, Marano J, Waldman A, Klinger A, Reinhold JM, Lahondère C, Weger-Lucarelli J. American Aedes japonicus japonicus, Culex pipiens pipiens, and Culex restuans mosquitoes have limited transmission capacity for a recent isolate of Usutu virus. Virology. 2021 Mar. DOI: 10.1016/j.virol.2020.12.023. 
• Bates TA, Chuong C, Hawks SA, Rai P, Duggal NK, Weger-Lucarelli J. Development and characterization of infectious clones of two strains of Usutu virus. Virology. 2021 Feb. DOI: 10.1016/j.virol.2020.12.004. 

Presentations

• Rai P, Webb EM, Paulson SL, Kang Lin, Lucarelli JW. 2024. Determine the impact of obese bloodmeal on alphavirus transmission and mosquito immune response. CeZAP Thematic Social Friday, Blacksburg, VA.
• Rai P, Marano JM, Kang L, Coutermarsh-Ott S, Weger-Lucarelli J. 2023. Using mouse coronavirus to determine the impact of obesity on coronavirus disease severity and identify biomarkers of severe disease outcome. American Society for Virology, Athens, GA, and Center for Emerging Zoonotic and Arthropod-borne pathogens (CeZAP) symposium, Blacksburg, VA.
• Rai P, Lucarelli JW. 2022. Determining the role of obesity on the transmission of chikungunya virus by mosquitoes. Biomedical and Veterinary Sciences seminar, Virginia Maryland College of Veterinary Medicine, VA.
• Rai P, Chuong C, Weger-Lucarelli J. 2022. Adenovirus transduction to express human ACE2 causes obesity-specific morbidity in mice, impeding studies on the effect of host nutritional status on SARS-CoV-2 pathogenesis. Biomedical and Veterinary Sciences Symposium, Virginia Maryland College of Veterinary Medicine, VA.
• Rai P, Weger-Lucarelli J. 2022. Determine the role of obesity on the transmission of chikungunya virus by Aedes aegypti mosquitoes. Virology World Conference, Rome, Italy.
• Rai P, Weger-Lucarelli J. 2022.Determine the role of alphavirus-infected obese bloodmeal on vector competence and mosquito immune response. American Society for Microbiology, Middletown, VA.
• Rai P, Webb EM, Weger-Lucarelli J. 2022. Insulin reduces alphavirus infection of Aedes aegypti mosquitoes by influencing vector immune pathways. Virginia Mosquito Control Association, Virginia Beach, VA.

Examination Graduate Committee

Major Advisor/Chair:

James Weger-Lucarelli, PhD
Assistant Professor
Department of Biomedical Sciences and Pathobiology VA-MD College of Veterinary Medicine 

Graduate Advising Committee Members:

Sally L. Paulson, PhD
Associate Professor
Veterinary and Medical Entomology

Nisha K. Duggal, PhD
Associate Professor
Department of Biomedical Sciences and Pathobiology VA-MD College of Veterinary Medicine

Tanya LeRoith, DVM, PhD, DACVP
Clinical Professor
Department of Biomedical Sciences and Pathobiology VA-MD College of Veterinary Medicine