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

• Published in: Viruses 2019-10, Vol.11 (10), p.972
• Main Authors: Cheng, Jinlong, Zhao, Ye, Xu, Gang, Zhang, Keran, Jia, Wenfeng, Sun, Yali, Zhao, Jing, Xue, Jia, Hu, Yanxin, Zhang, Guozhong
• Format: Article
• Language: English
• Subjects: adsorption; blood serum; Blood-brain barrier; Bronchitis; chickens; coronavirus; Coronaviruses; Encephalitis; Furin; furin-s2′ site; genotype; Genotypes; infectious bronchitis; Infectious bronchitis virus; Middle East respiratory syndrome; mortality; Mutants; mutation; neurotropism; neutralization tests; Pathogenicity; peptides; Poultry; qx type; Respiratory diseases; Spike protein; vaccines; virion; Virions; viruses
• ISSN: 1999-4915; 1999-4915
• 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.