The SARS-CoV-2 Spike is a Virulence Determinant and Plays a Major Role on the Attenuated Phenotype of Omicron Virus in a Feline Model of Infection

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2024 Feb 29

PMID 38421180

Authors

Mathias Martins

Mohammed Nooruzzaman

Jessie Lee Cunningham

Chengjin Ye

Leonardo Cardia Caserta

Nathaniel Jackson

Luis Martinez-Sobrido

Ying Fang

Diego G Diel

Affiliations

Soon will be listed here.

Abstract

Importance: We have demonstrated that the Omicron BA.1.1 variant presents lower pathogenicity when compared to D614G (B.1) lineage in a feline model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are over 50 mutations across the Omicron genome, of which more than two-thirds are present in the Spike (S) protein. To assess the role of the Omicron BA.1 S on virus pathogenesis, recombinant viruses harboring the S D614G mutation (rWA1-D614G) and the Omicron BA.1 Spike gene (rWA1-Omi-S) in the backbone of the ancestral SARS-CoV-2 WA1 were generated. While the Omicron BA.1 S promoted early entry into cells, it led to impaired fusogenic activity and cell-cell spread. Infection studies with the recombinant viruses in a relevant naturally susceptible feline model of SARS-CoV-2 infection here revealed an attenuated phenotype of rWA1-Omi-S, demonstrating that the Omi-S is a major determinant of the attenuated disease phenotype of Omicron strains.

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