Virginia Research Day 2025

Medical Student Research Biomedical

16 SARS-CoV-2 Targets Gap Junction Intercellular Communication to Facilitate Viral Replication

Julia Kawas; Michael Zeitz; Eric Sapp; Karim Abouelenein; Chelsea Phillips; Rachel Padget; James Smyth Corresponding author: jkawas@vt.vcom.edu Edward Via College of Osteopathic Medicine Fralin Biomedical Research Institute at Virginia Tech Carilion Center for Vascular and Heart Research, FBRI at VTC Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech Virginia Tech Carilion School of Medicine; Department of Biological Sciences, Virginia Tech

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, can cause a broad spectrum of disease severity and types ranging from respiratory distress to cardiac and neurologic dysfunction. The cell-intrinsic antiviral response is triggered by cytosolic viral dsRNA during SARS-CoV-2 infection and elicits the interferon response to perturb viral replication and spread. Gap junctions, comprising the protein connexin43 (Cx43), propagate the antiviral response to neighboring uninfected cells through direct coupling of cytoplasms. Other viruses, such

as adenovirus, have been demonstrated to target gap junction function and dampen the spread of this antiviral response though activation of PKC signaling to phosphorylate Cx43 at serine368 and cause gap junction closure. How SARS-CoV-2 may target gap junction function is unknown. We hypothesized that SARS-CoV-2-encoded proteins suppress intercellular communication through activation of PKC and subsequent phosphorylation of Cx43. We will transiently express individual

SARS-CoV-2 proteins in human epithelial cells and measure induction and measure phosphorylation of Cx43 serine368 phosphorylation by western blotting. The effects on gap junction function from positive candidate genes will be determined using the lucifer yellow dye spread. This work will identify critical SARS-CoV-2 proteins involved in limiting antiviral immune responses and identify molecular targets for therapeutic intervention during coronavirus infection.

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2025 Research Recognition Day