Abstract
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.
Highlights
Coronaviruses (CoVs) are single-strand plus RNA viruses, which belong to the order Nidovirales.CoVs normally infect epithelial cells such as respiratory epithelial cells, intestinal epithelial cells and kidney epithelial cells, which causes respiratory or intestinal tract diseases with various levels of severity [1,2]
Is an infectious molecular clone of Infectious bronchitis virus (IBV)-YN strain (GenBank accession number: JF893452), which grows in Chicken embryo kidney (CEK) cells [26]. rYN-S2/RRKR is an infectious molecular clone of the IBV-YN strain whose sequence
The results of this study first demonstrated that a furin cleavage site immediately upstream of the fusion peptide in the S protein of QX genotype (QX-type) IBV is related to the pathogenesis of IBV in brain
Summary
CoVs normally infect epithelial cells such as respiratory epithelial cells, intestinal epithelial cells and kidney epithelial cells, which causes respiratory or intestinal tract diseases with various levels of severity [1,2]. Human coronavirus OC43 (HCoV-OC43) can reach the central nervous system (CNS) by intranasal inoculation in BALB/c mice, which causes encephalitis [8,9,10,11]. Infectious bronchitis virus (IBV) belongs to the gamma-coronavirus group (γ-CoV), which causes a highly contagious, acute viral respiratory disease of chickens that has caused great economic losses in the poultry industry. Because of severe damage of respiratory mucosa, infected chickens are susceptible to secondary infection by mycoplasma, bacteria, or other pathogens causing high mortality
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