Abstract
Equine influenza viruses (EIVs) of H3N8 subtype are culprits of severe acute respiratory infections in horses, and are still responsible for significant outbreaks worldwide. Adaptability of influenza viruses to a particular host is significantly influenced by their codon usage preference, due to an absolute dependence on the host cellular machinery for their replication. In the present study, we analyzed genome-wide codon usage patterns in 92 EIV strains, including both H3N8 and H7N7 subtypes by computing several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis disclosed bias of preferred synonymous codons towards A/U-ended codons. The overall codon usage bias in EIVs was slightly lower, and mainly affected by the nucleotide compositional constraints as inferred from the RSCU and effective number of codon (ENc) analysis. Our data suggested that codon usage pattern in EIVs is governed by the interplay of mutation pressure, natural selection from its hosts and undefined factors. The H7N7 subtype was found less fit to its host (horse) in comparison to H3N8, by possessing higher codon bias, lower mutation pressure and much less adaptation to tRNA pool of equine cells. To the best of our knowledge, this is the first report describing the codon usage analysis of the complete genomes of EIVs. The outcome of our study is likely to enhance our understanding of factors involved in viral adaptation, evolution, and fitness towards their hosts.
Highlights
Equine influenza viruses (EIVs) are negative-sense, single-stranded, segmented RNA viruses within the family Orthomyxoviridae, and are a common cause of respiratory infections in horses
It is evident from the initial nucleotide composition analysis that A/U-ended codons might be preferred over G/C-ended codons in the EIV genomes
This study conclusively demonstrates that genome-wide codon usage patterns in EIVs are deciphered by the interplay of different determinant factors like mutation pressure, natural selection, Aromo values, genome length and undefined factors, though their dynamics may be complex
Summary
Equine influenza viruses (EIVs) are negative-sense, single-stranded, segmented RNA viruses within the family Orthomyxoviridae, and are a common cause of respiratory infections in horses. The most striking feature of influenza viruses is their ability to evade the host immune response either by antigenic shift or reassortment [4,5]. They undergo rapid evolution when subjected to host immune selection pressure, especially while crossing the host species barrier [6]. A detailed understanding of factors responsible for the EIVs codon usage preferences will help in delineating their evolution, and the relationship with the host immune response
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