National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI158186
米国
引用
ジャーナル: Nature / 年: 2025 タイトル: Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kinetics. 著者: M Alejandra Tortorici / Annette Choi / Cecily A Gibson / Jimin Lee / Jack T Brown / Cameron Stewart / Anshu Joshi / Sheri Harari / Isabelle Willoughby / Catherine Treichel / Elizabeth M Leaf ...著者: M Alejandra Tortorici / Annette Choi / Cecily A Gibson / Jimin Lee / Jack T Brown / Cameron Stewart / Anshu Joshi / Sheri Harari / Isabelle Willoughby / Catherine Treichel / Elizabeth M Leaf / Jesse D Bloom / Neil P King / Christine Tait-Burkard / Gary R Whittaker / David Veesler / 要旨: The ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat. FCoV-23 is a recently emerged, highly pathogenic recombinant ...The ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat. FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis. Here we report cryogenic electron microscopy structures of two FCoV-23 spike isoforms that correspond to the in-host loss of domain 0 observed in clinical samples. The loss of domain 0 markedly enhances the fusogenicity and kinetics of entry into cells and possibly enables biotype switching and lethality. We show that FCoV-23 can use several aminopeptidase N orthologues as receptors and reveal the molecular determinants of receptor species tropism, including a glycan that modulates human receptor engagement. We define antigenic relationships among alphacoronaviruses that infect humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody that inhibits FCoV-23 entry. Our results pave the way for the development of vaccines and therapeutics that target this highly pathogenic virus.