“The SPARK program has provided an invaluable experience for me. I improved my communication and research skills and learned to budget for a project, which as a trainee, you often don’t get to do. I will use the communication and research skills I have learned through this program as I prepare for future speaking engagements and apply for funding.”
2024 Tullie and Rickey Families Spark Awards Winner
Rimjhim Agarwal
Does chronic chikungunya infection resemble an autoimmune disease?
Funded: January 2024
Funded by: The generosity of the Rosemary Kraemer Raitt Foundation Trust
We need to understand why so many people infected with Chikungunya virus (CHIKV) develop chronic, arthritis-like disease. My SPARK project investigates if this mysterious arthritis-like disease resembles an autoimmune disease. I am examining whether T helper cells, a type of immune cell, may mistakenly begin to attack a person’s own cells instead of taking aim at targets on CHIKV.
Using bioinformatics, I identified 15 self-antigens (sites on healthy cells) with high sequence similarity to CHIKV antigens (sites on the virus). I then stimulated T helper cells from chronic CHIKV patients with these self-antigens.
I found no immune response, suggesting no cross-reactivity; however, this finding doesn’t rule out the possibility that T helper cells are mistaking healthy cells for viral targets. As a next step, I will further investigate by comparing the entire CHIKV proteome with the human proteome to find better sequence matches. I will also test for T helper cell cross-reactivity with other viruses, such as cytomegalovirus and Epstein-Barr virus. Understanding the role of T helper cells in chronic CHIKV disease could lead to better vaccines and treatments for people affected with virus-induced autoimmune diseases around the world.
What was the goal of your SPARK project?
Chikungunya virus (CHIKV) is a mosquito-borne pathogen that has been reported in more than 110 countries. We need to understand why so many people infected with CHIKV develop chronic, arthritis-like disease. This mysterious disease resembles an autoimmune disease and leads to severe joint pain and tissue damage. Using patient samples, I examined whether T helper cells, a type of immune cell, may trigger joint pain by mistakenly attacking a person’s own cells instead of targeting CHIKV. My goal was to deepen our understanding of long-lasting effects of CHIKV infection and contribute to the development of new therapeutics.
SPARK Project Results
I used bioinformatics tools to identify 15 self-antigens (sites on healthy cells) with high sequence similarity to CHIKV antigens (sites on the virus). I then stimulated T helper cells from chronic CHIKV patients with these self-antigens. My goal was to test if these virus-fighting T helper cells would cross-react to markers from healthy cells. I found no immune response, suggesting that the patients’ T helper cells were not cross-reactive; however, this finding doesn’t rule out the possibility that T helper cells are mistaking healthy cells for viral targets. My research also revealed which molecular sites on CHIKV trigger the strongest T cell responses. Understanding this T cell “avidity” may prove important for future investigations into the roles of T cells during CHIKV infection.
What’s next for this project?
I am excited to follow up on my SPARK project by studying CHIKV-specific CD4+ T cells in greater depth. I plan to use high-throughput transcriptomic tools and TCR analysis to learn more about how these cells target CHIKV antigens. I can then compare CD4+ T cells from individuals with chronic CHIKV disease with cells from individuals who have recovered after CHIKV infection. This work may shed light on how specific T cell subsets lead to chronic, arthritis-like symptoms. CHIKV is not the only virus that can trigger chronic, arthritis-like disease. I also plan to study T helper cell cross-reactivity with other viruses, such as cytomegalovirus and Epstein-Barr virus.
What’s next for Rimjhim?
My goal is to successfully finish my Ph.D. and potentially pursue a career in academia post graduation. I really enjoy studying host-viral interactions and hope to continue that in the future. Currently as a Ph.D. student, I am hoping to defend my thesis work in the next two years and apply for postdoctoral positions in the field of infectious diseases. I have two manuscripts under review which is a major milestone in my Ph.D. journey. I am really excited to see how my thesis project advances in the coming years!
