tetano
Editor, Senior Moderator
Nat Commun
. 2026 Jul 20.
doi: 10.1038/s41467-026-74676-8. Online ahead of print.
Viral syncytia evolve to resist interferon
Tiansheng Li[SUP] 1 [/SUP], Insung Kang[SUP] 2 [/SUP], Juan Ye[SUP] 3 [/SUP], Zhe Hu[SUP] 4 [/SUP], James Gibbs[SUP] 4 [/SUP], Chengjin Ye[SUP] 5 [/SUP], Kazuyo Takeda[SUP] 6 [/SUP], Ivan Kosik[SUP] 4 [/SUP], Guoli Shi[SUP] 7 [/SUP], Jaroslav Holly[SUP] 4 [/SUP], Martina Kosikova[SUP] 2 [/SUP], Zhiping Ye[SUP] 2 [/SUP], Alex A Compton[SUP] 7 [/SUP], Luis Martinez-Sobrido[SUP] 5 [/SUP], Reed F Johnson[SUP] 8 [/SUP], Hang Xie[SUP] 2 [/SUP], Jonathan W Yewdell[SUP] 9 [/SUP]
Affiliations
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.
. 2026 Jul 20.
doi: 10.1038/s41467-026-74676-8. Online ahead of print.
Viral syncytia evolve to resist interferon
Tiansheng Li[SUP] 1 [/SUP], Insung Kang[SUP] 2 [/SUP], Juan Ye[SUP] 3 [/SUP], Zhe Hu[SUP] 4 [/SUP], James Gibbs[SUP] 4 [/SUP], Chengjin Ye[SUP] 5 [/SUP], Kazuyo Takeda[SUP] 6 [/SUP], Ivan Kosik[SUP] 4 [/SUP], Guoli Shi[SUP] 7 [/SUP], Jaroslav Holly[SUP] 4 [/SUP], Martina Kosikova[SUP] 2 [/SUP], Zhiping Ye[SUP] 2 [/SUP], Alex A Compton[SUP] 7 [/SUP], Luis Martinez-Sobrido[SUP] 5 [/SUP], Reed F Johnson[SUP] 8 [/SUP], Hang Xie[SUP] 2 [/SUP], Jonathan W Yewdell[SUP] 9 [/SUP]
Affiliations
- PMID: 42477325
- DOI: 10.1038/s41467-026-74676-8
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.