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bioRxiv · 10.1101/2023.11.20.567927

Human coronavirus OC43 infection remodels Connexin 43 mediated gap junction intercellular communication in vitro

Karmakar, S.·Das Sarma, J.
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Abstract

{beta}-coronaviruses cause acute infection in the upper respiratory tract, resulting in various symptoms and clinical manifestations. OC43 is a human {beta}-coronavirus that induces mild clinical symptoms and can be safely studied in the BSL2 laboratory. Due to its low risk, OC43 can be a valuable and accessible model for understanding {beta}-coronavirus pathogenesis. One potential target for limiting virus infectivity could be gap junction-mediated communication. This study aims to unveil the status of cell-to-cell communications through gap junctions in human {beta}-coronavirus infection. Infection with OC43 leads to reduced expression of Cx43 in A549, a lung epithelial carcinoma cell line. Infection with this virus also showed a significant ER and oxidative stress increase. Internal localization of Cx43 is observed post OC43 infection in the ERGIC region, which impairs the gap junction communication between two adjacent cells, confirmed by Lucifer yellow dye transfer assay. It also affects hemichannel formation, as depicted by the EtBr uptake assay. Altogether, these results suggest that several physiological changes accompany OC43 infection in A549 cells and can be considered an appropriate model system for understanding the differences in gap junction communication post-viral infections. This model system can provide valuable insights for developing therapies against human {beta}-coronavirus infections. ImportanceThe enduring impact of the recent SARS-CoV-2 pandemic underscores the importance of studying human {beta}-coronaviruses, advancing our preparedness for future coronavirus infections. Due to SARS-CoV-2 being highly infectious, another human {beta}-coronavirus OC43 can be considered as an experimental model. One of the crucial pathways that can be considered is gap junction communication, as it is vital for cellular homeostasis. Our study seeks to understand the change in Cx43-mediated cell-to-cell communication during human {beta}-coronavirus OC43 infection. In vitro studies showed the downregulation of the gap junction protein Cx43 and the upregulation of endoplasmic reticulum and oxidative stress markers post-OC43 infection. Furthermore, OC43 infection causes impairment of functional hemichannel and gap junction formation. Overall, this current study infers that OC43 infection reshapes intercellular communication, suggesting that this pathway may be a promising target for designing highly effective therapeutics against human coronaviruses by regulating Cx43 expression.

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Karmakar, S., Das Sarma, J.. 2023-11-21. Human coronavirus OC43 infection remodels Connexin 43 mediated gap junction intercellular communication in vitro. https://doi.org/10.1101/2023.11.20.567927

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