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Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development

Natalia Goñi1, Andrés Iriarte23, Victoria Comas1, Martín Soñora1, Pilar Moreno14, Gonzalo Moratorio15, Héctor Musto2 and Juan Cristina1*

Author Affiliations

1 Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, 11400, Uruguay

2 Laboratorio de Organización y Evolución del Genoma, Instituto de Biología, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, 11400, Uruguay

3 Laboratorio de Evolución, Instituto de Biología, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, 11400, Uruguay

4 Unidad de Proteínas Recombinantes, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, 11400, Uruguay

5 Unidad de Biofísica de Proteínas, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, 11400, Uruguay

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Virology Journal 2012, 9:263  doi:10.1186/1743-422X-9-263

Published: 8 November 2012

Abstract

Background

Influenza A virus (IAV) is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity. The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed.

Results

We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly influenced by underlying biases in base composition. When correspondence analysis (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process.

Conclusions

A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies. These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments. Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines.

Keywords:
Influenza A virus; Codon usage; Evolution