Revelation of Influencing Factors in Overall Codon Usage Bias of Equine Influenza Viruses

PLoS One. 2016 Apr 27;11(4):e0154376. doi: 10.1371/journal.pone.0154376. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics
  • Animals
  • Biological Evolution
  • Codon*
  • Gene Expression Regulation, Viral*
  • Genetic Code
  • Genome, Viral*
  • Horse Diseases / virology*
  • Horses
  • Host-Pathogen Interactions
  • Influenza A Virus, H3N8 Subtype / genetics*
  • Influenza A Virus, H3N8 Subtype / metabolism
  • Influenza A Virus, H7N7 Subtype / genetics*
  • Influenza A Virus, H7N7 Subtype / metabolism
  • Models, Statistical
  • Mutation Rate
  • Orthomyxoviridae Infections / veterinary*
  • Orthomyxoviridae Infections / virology
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism
  • Species Specificity
  • Virus Replication

Substances

  • Codon
  • RNA, Transfer

Grants and funding

The Indian Council of Agricultural Research, India provided the necessary funding for the research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.