Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry

Virology. 2006 Jul 5;350(2):358-69. doi: 10.1016/j.virol.2006.02.003. Epub 2006 Mar 7.

Abstract

The fusogenic potential of Class I viral envelope glycoproteins is activated by proteloytic cleavage of the precursor glycoprotein to generate the mature receptor-binding and transmembrane fusion subunits. Although the coronavirus (CoV) S glycoproteins share membership in this class of envelope glycoproteins, cleavage to generate the respective S1 and S2 subunits appears absent in a subset of CoV species, including that responsible for the severe acute respiratory syndrome (SARS). To determine whether proteolytic cleavage of the S glycoprotein might be important for the newly emerged SARS-CoV, we introduced a furin recognition site at single basic residues within the putative S1-S2 junctional region. We show that furin cleavage at the modified R667 position generates discrete S1 and S2 subunits and potentiates membrane fusion activity. This effect on the cell-cell fusion activity by the S glycoprotein is not, however, reflected in the infectivity of pseudotyped lentiviruses bearing the cleaved glycoprotein. The lack of effect of furin cleavage on virion infectivity mirrors that observed in the normally cleaved S glycoprotein of the murine coronavirus and highlights an additional level of complexity in coronavirus entry.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Fusion
  • Chlorocebus aethiops
  • Furin / metabolism*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Molecular Sequence Data
  • SARS Virus / physiology*
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / physiology*
  • Virion / genetics
  • Virion / physiology

Substances

  • Membrane Glycoproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • Furin