Glycan shield and fusion activation of a deltacoronavirus spike glycoprotein fine-tuned for enteric infections

Xiaoli Xiong, M. Alejandra Tortorici, Joost Snijder, Craig Yoshioka, Alexandra C. Walls, Wentao Li, Andrew T. McGuire, Félix A. Rey, Berend Jan Bosch, David Veesler

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome. They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection. The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response. We report here the 3.5-Å-resolution cryoelectron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus. Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts. The structure further reveals a shortened S 2 ' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant. This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.

Original languageEnglish (US)
Article numbere01628-17
JournalJournal of virology
Volume92
Issue number4
DOIs
StatePublished - Feb 1 2018

Keywords

  • Coronaviruses
  • Cryo-EM
  • Fusion proteins

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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