Presenter(s)

Malabika Bhowmik, Tooba Momin

Comments

3:00-4:15, Kennedy Union Ballroom

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Description

Objective: RNA viruses exhibit high mutation rates, enhancing their survival and potential for cross-species transmission, making them strong candidates for future pandemics. Targeting conserved aspects of viral replication could be an effective antiviral strategy. ZFP36L1, a CCCH-type zinc finger protein that regulates mRNA turnover, has demonstrated antiviral activity against several RNA viruses. Our study investigates the mechanism by which ZFP36L1 suppresses human coronavirus OC43 (HCoV-OC43) replication and explores sodium butyrate as a potential enhancer of ZFP36L1 expression to amplify its antiviral effects. Methods: Wild-type (WT), ZFP36L1-overexpressing (OE), and ZFP36L1 knockdown (KD) HCT-8 cells were infected with HCoV-OC43 and analyzed for viral titers, cytopathic effects, and viral transcript levels via qPCR. To assess whether poly(A) tail deadenylation contributes to viral suppression, CNOT1 was knocked down in OE cells, and viral titers were measured. Computational RNA-protein interaction tools (RPISeq) and homology modeling identified potential interactions between ZFP36L1 and the viral genome, validated through RNA immunoprecipitation and luciferase reporter assays. Additionally, sodium butyrate was tested for its ability to enhance ZFP36L1 expression, followed by viral titer assessment. Results: ZFP36L1 overexpression significantly reduced HCoV-OC43 titers, while knockdown increased viral replication (p less than 0.05). CNOT1 knockdown in OE cells did not reverse suppression, suggesting a poly(A)-independent mechanism. ZFP36L1 strongly interacted with the HCoV-OC43 nucleocapsid protein, leading to suppressed viral replication. Sodium butyrate treatment upregulated ZFP36L1 expression, further reducing viral titers. Conclusions: ZFP36L1 suppresses HCoV-OC43 replication by interacting with the viral nucleocapsid protein, independent of poly(A) tail deadenylation. Sodium butyrate enhances ZFP36L1 expression, strengthening its antiviral effects and leading to a greater reduction in viral titers. This highlights the potential of targeting ZFP36L1 expression via biocompatible compounds like sodium butyrate as a novel antiviral strategy against human coronaviruses, including SARS-CoV and SARS-CoV-2.

Publication Date

4-23-2025

Project Designation

Graduate Research

Primary Advisor

Mrigendra Rajput

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Institutional Learning Goals

Scholarship; Scholarship; Scholarship

ZFP36L1 Suppresses Human Coronavirus OC43 Replication Independent of Poly(A) Tail Deadenylation

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