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Syncytia Formation Promotes Virus Resistance to Interferon and Neutralizing Antibodies

Li, T.; Kang, I.; Hu, Z.; Gibbs, J.; Ye, C.; Kosik, I.; Shi, G.; Holly, J.; Kosikova, M.; Compton, A. A.; Martinez-Sobrido, L.; Johnson, R.; Hang, X.; Yewdell, J. W.

2023-12-13 microbiology
10.1101/2023.12.12.571262 bioRxiv
Show abstract

SARS-CoV-2, like many viruses, generates syncytia. Using SARS-CoV-2 and S (S) expressing recombinant vesicular stomatitis and influenza A viruses, we show that S-mediated syncytia formation provides resistance to interferons in cultured cells, human small airway-derived air-liquid interface cultures and hACE2 transgenic mice. Amino acid substitutions that modulate fusogenicity in Delta- and Omicron-derived S have parallel effects on viral interferon resistance. Syncytia formation also decreases antibody virus neutralization activity in cultured cells. These findings explain the continued selection of fusogenic variants during SARS-CoV-2 evolution in humans and, more generally, the evolution of fusogenic viruses despite the adverse effects of syncytia formation on viral replication in the absence of innate or adaptive immune pressure.

Published in Nature Communications (predicted rank #1) · training set

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