The S2 Subunit of QX-type Infectious Bronchitis Coronavirus Spike Protein Is an Essential Determinant of Neurotropism

Viruses. 2019 Oct 22;11(10):972. doi: 10.3390/v11100972.


Some coronaviruses (CoVs) have an extra furin cleavage site (RRKR/S, furin-S2' site) upstream of the fusion peptide in the spike protein, which plays roles in virion adsorption and fusion. Mutation of the S2' site of QX genotype (QX-type) infectious bronchitis virus (IBV) spike protein (S) in a recombinant virus background results in higher pathogenicity, pronounced neural symptoms and neurotropism when compared with conditions in wild-type IBV (WT-IBV) infected chickens. In this study, we present evidence suggesting that recombinant IBV with a mutant S2' site (furin-S2' site) leads to higher mortality. Infection with mutant IBV induces severe encephalitis and breaks the blood-brain barrier. The results of a neutralization test and immunoprotection experiment show that an original serum and vaccine can still provide effective protection in vivo and in vitro. This is the first demonstration of IBV-induced neural symptoms in chickens with encephalitis and the furin-S2' site as a determinant of neurotropism.

Keywords: QX type; coronavirus; encephalitis; furin-S2′ site; infectious bronchitis virus; neurotropism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Blood-Brain Barrier / virology
  • Chickens / virology
  • Coronavirus Infections / veterinary*
  • Coronavirus Infections / virology
  • Encephalitis, Viral / veterinary*
  • Furin / genetics
  • Infectious bronchitis virus / chemistry*
  • Infectious bronchitis virus / genetics
  • Infectious bronchitis virus / physiology
  • Mutation
  • Neurons / virology*
  • Specific Pathogen-Free Organisms
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / genetics
  • Viral Tropism*


  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • Furin