Spike glycoprotein cleavage recognition site analysis of infectious bronchitis virus

The spike glycoprotein of infectious bronchitis virus (IBV), a coronavirus, is translated as a precursor protein (S,), then cleaved into two subunits (S1 and S2) by host cell serine proteases. In this study, we compared the c leavage recognition site of 55 IBV isolates to determine if the cleavage re cognition site sequence, which consists of five basic amino acid residues, correlates with host cell range, serotype, geographic origin, and pathogeni city as it: does in orthomyxoviruses and paramyxoviruses. The most common c leavage recognition site observed (33 of 55 viruses) was Arg-Arg-Ser-Arg-Ar g, representing at least 11 different serotypes. Thus, cleavage recognition sire does not appear to correlate with serotype. We also determined that c leavage recognition site sequence does not: correlate with pathogenicity be cause attenuated and pathogenic isolates (different passages of the same vi rus) contain identical cleavage recognition site sequences. In addition, ne phropathogenic strains had the same cleavage recognition site sequence as m any nonnephropathogenic isolates. Cleavage recognition sire sequence does c orrelate with viruses in different geographic regions, which may be an impo rtant characteristic to examine in epidemiologic studies. An IBV monoclonal antibody neutralization-resistant mutant (NR 18) had an unusual substituti on of Ile for Arg at the fourth position, giving the sequence Arg-Arg-Ser-I le-Arg, which likely prevents cleavage and, thus, destroys the conformation ally dependent monoclonal antibody binding epitope. Six residues on the ami no-terminal side of the cleavage recognition sire are conserved in 31% of t he isolates and consist of only one or two basic amino acids. Thus, the num ber of basic residues around the cleavage recognition site does not appear to correlate with increased cleavability, host cell range, and increased vi rulence as it does with envelope glycoproteins in orthomyxoviruses and para myxoviruses.