A human coronavirus OC43 variant harboring persistence-associated mutations in the S glycoprotein differentially induces the unfolded protein response in human neurons as compared to wild-type virus.

ABSTRACT: We have reported that human respiratory coronavirus OC43 (HCoV-OC43) is neurotropic and neuroinvasive in humans and mice, and that neurons are the primary target of infection in mice, leading to neurodegenerative disabilities. We now report that an HCoV-OC43 mutant harboring two persistence-associated S glycoprotein point mutations (H183R and Y241H), induced a stronger unfolded protein response (UPR) and translation attenuation in infected human neurons. There was a major contribution of the IRE1/XBP1 pathway, followed by caspase-3 activation and nuclear fragmentation, with no significant role of the ATF6 and eIF2-alpha/ATF4 pathways. Our results show the importance of discrete molecular viral S determinants in virus-neuronal cell interactions that lead to increased production of viral pro

SUBMITTER: Favreau DJ 

PROVIDER: S-EPMC7111944 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature