BETACORONAVIRUSES DIFFERENTIALLY ACTIVATE THE INTEGRATED STRESS RESPONSE TO OPTIMIZE VIRAL REPLICATION IN LUNG DERIVED CELL LINES.

ABSTRACT: The betacoronavirus genus contains five of the seven human viruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus- HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus) and MERS-CoV (merbecovirus)- to study betacoronavirus interaction with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation in lung derived cell lines. We demonstrate that MERS-CoV, HCoV-OC43, and SARS-CoV-2 all activate PERK and induce responses downstream of p-eIF2α, while only SARS-CoV

SUBMITTER: Renner DM 

PROVIDER: S-EPMC11463420 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature