AI Summary
The article discusses the virological characteristics of the Omicron XBB.1.5 variant of the SARS-CoV-2 virus. The variant evolved from XBB.1 by acquiring the S486P spike mutation and a nonsense mutation in ORF8. Neutralization assays showed similar immune escape abilities between XBB.1.5 and XBB.1. The study also examines the structural basis for the interaction between the S protein of XBB.1.5 and human ACE2. It provides insights into the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters and the impairment of MHC suppression caused by the ORF8 nonsense mutation. In vivo experiments with recombinant viruses suggest that the XBB.1.5 mutations are associated with reduced virulence. Overall, the study identifies the viral functions that differentiate XBB.1 and XBB.1.5.
Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), continues to circulate among humans, leading to the emergence of new variants. Our series of studies aiming to characterize SARS-CoV-2 variants1,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Saito, A. et al. Virological characteristics of