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Updated: Aug 6, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Viral syncytia evolve to resist interferon
Tiansheng Li1, Insung Kang2, Juan Ye3
1Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA. tiansheng.li@nih.gov.
Abstract:
SARS-CoV-2, like many viruses, generates syncytia but the role of syncytia formation in viral evolution remains unknown. Using SARS-CoV-2 and SARS-CoV-2 Spike (S) replacement vesicular stomatitis (VSV), we show that S-mediated syncytia impair the antiviral effects of interferons in cultured cells, human lung cell cultures, and hACE2 transgenic mice. Amino acid substitutions that modulate syncytia formation in Delta- and Omicron-encoded S have parallel effects on viral interferon resistance. S-mediated syncytia compromise antibody-mediated virus neutralization in cultured cells. We recapitulate interferon and neutralizing antibody resistance in syncytia generated by the orthoreovirus p14 fusion-associated small transmembrane (FAST) protein in VSV, influenza virus, and seasonal coronavirus OC43 infections. These findings explain selection of SARS-CoV-2 fusogenic variants in humans and, more generally, the evolution of fusogenic viruses driven by adaptive and innate immunity.
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