article · Nature Communications
Circulation of the SARS-CoV-2 Omicron subvariant XBB led to the emergence of XBB.1.5, which has been designated a Variant of Interest. Phylogenetic examination indicates that XBB.1.5 originated from XBB.1 through the acquisition of an ORF8 nonsense mutation followed by the S486P spike mutation. Experimental neutralisation assays reveal that XBB.1.5 retains an immune escape capability comparable to that of XBB.1. In addition, structural evaluations demonstrate that the spike proteins of both variants share similar conformations when interacting with the human ACE2 receptor. In vivo assessments using recombinant viruses in hamsters establish that the specific mutations found in XBB.1.5 lead to lower virulence. Crucially, the ORF8 nonsense mutation impairs the ability of XBB.1.5 to suppress the major histocompatibility complex, clarifying the functional differences between these viral lineages.
Tracking how emerging SARS-CoV-2 lineages evolve is critical for public health monitoring and understanding changes in disease severity. This research explains why XBB.1.5 differs from predecessor variants by showing how specific mutations affect immune recognition mechanisms and reduce virulence in animal models, providing a clearer biological picture of ongoing viral evolution.
This work represents early-stage basic virology research. While the findings provide precise structural and functional data that could assist pharmaceutical developers and diagnostic researchers in monitoring variant characteristics, the abstract does not indicate an immediate application pathway or direct commercial product.
AI-generated from the published abstract. Always read the original work before citing.
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.
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.1038/s41467-024-45274-3
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
