Description
- Abstract:
- Abstract of Uncovering and Characterizing the Function and Utility of Human Norovirus NS1, by Vasisht Varma Poosapati, ScM, Brown University, May 2026. Human norovirus (hNoV) is a leading cause of acute viral gastroenteritis worldwide, yet the molecular mechanisms by which it evades host innate immune responses remain incompletely defined. In this study, we investigated the role of the hNoV non-structural protein NS1 in modulating antiviral signaling, with a focus on MDA5-dependent pathways that drive interferon production. Using a reporter-based system in HEK293T cells, we demonstrate that NS1 proteins derived from both GI and GII genogroups suppress antiviral signaling in a dose-dependent manner. This activity is further conserved in murine norovirus, supporting a broadly conserved mechanism of immune evasion. Functional assays revealed that NS1 does not inhibit signaling induced by exogenous interferons, indicating that suppression occurs upstream of interferon receptor engagement. These findings support a model in which NS1 targets intracellular antiviral sensing pathways rather than acting through cytokine neutralization. Domain mapping identified the N-terminal region of NS1 as necessary and sufficient for suppressive activity. Notably, a minimal 16-amino acid segment retained robust function, indicating that immune evasion is mediated by a compact and conserved interface. Together, these findings establish NS1 as a conserved antagonist of MDA5-dependent antiviral responses and provide a foundation for future studies aimed at identifying host targets and defining mechanisms of immune evasion.
- Notes:
- Thesis (Sc. M.)--Brown University, 2026
Citation
Poosapati, Vasisht Varma,
"Uncovering and Characterizing the Function and Utility of Human Norovirus NS1"
(2026).
Biology and Medicine Theses and Dissertations, Biotechnology.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:h9yyxv5h/
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Biology and Medicine Theses and Dissertations
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