Abstract
BackgroundThe influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease.ResultsRelative Synonymous Codon Usage (RSCU) values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA). The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through in toto transfer of an avian influenza virus.Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes.ConclusionsCodon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.
Highlights
The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century
Since 1997 avian H5N1 influenza has been infecting humans zoonotically resulting in a high mortality rate [3] and there were fears it might cause the first pandemic of this century
The influenza pandemics in the last century were caused through antigenic shift, which occurs when there is a reassortment of the surface protein segments between viruses, resulting in a virus that was immunologically novel to humans [7]
Summary
The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host’s machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease. In order to evade the host immune response, human seasonal influenza virus changes its antigenicity by introducing novel mutations in its surface proteins (called antigenic drift) [6]. The influenza pandemics in the last century were caused through antigenic shift, which occurs when there is a reassortment of the surface protein segments between viruses, resulting in a virus that was immunologically novel to humans [7]. To better prepare for future pandemics, a detailed understanding of the basic biology of this virus, especially its evolution and methods for host adaptation, is needed
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