Molecular and biological basis of genetic variability of the infectious bronchitis virus in chickens

Coronaviruses are a family of enveloped viruses with a single-stranded positive-sense RNA genome ranging from 26 to 36 thousand base pairs in length. Their distinctive feature is the ability to synthesize "nested" subgenomic RNAs, which ensures gene expression in the absence of classical promoters. The causative agent of infectious bronchitis virus (IBV) belongs to the gammacoronaviruses and causes a highly contagious disease affecting the respiratory, reproductive, and urinary systems. Morbidity reaches 100%, and mortality in complicated cases can be up to 60%. The IBV genome is organized according to the scheme 5'UTR-1a/1ab-S-3a-3b-E-M-5a-5b-N-3'UTR. The major part of the genome is occupied by open reading frames ORF1a and ORF1b, which are translated into polyproteins pp1a and pp1ab. Proteolytic cleavage results in the formation of 16 non-structural proteins (nsp1–nsp16) that assemble into the replicase-transcriptase complex. Key functions of the complex include RNA-dependent RNA polymerase activity (nsp12), helicase activity (nsp13), error correction (nsp14), immune response suppression (nsp3, nsp15), and transcript capping (nsp16). The second part of the genome encodes structural proteins S, M, E, and N. Genetic diversity of IBV is driven by mutations (point substitutions, deletions, insertions) and recombination via the copy-choice mechanism. Template switching occurs at transcription-regulatory sequences (TRS), ensuring the synthesis of subgenomic mRNAs. A side consequence of this process is recombination between different genomes during coinfection. Recombination hotspots have been identified in the genes encoding nsp2, nsp3, nsp8, nsp12, and in the S protein gene, which may affect pathogenicity and the virus's ability to evade immunity.