Phylogenetic Diversity and Genotypical Complexity of H9N2 Influenza A Viruses Revealed by Genomic Sequence Analysis

Guoying Dong,Thomas Jude Deliberto,Guangju Ji,Hongxuan He,Chengmin Wang,Jing Luo,Hong Zhang,Mingxing Duan,Dale Louis Nolte,Justin Brown

doi:10.1371/journal.pone.0017212

Abstract

H9N2 influenza A viruses have become established worldwide in terrestrial poultry and wild birds, and are occasionally transmitted to mammals including humans and pigs. To comprehensively elucidate the genetic and evolutionary characteristics of H9N2 influenza viruses, we performed a large-scale sequence analysis of 571 viral genomes from the NCBI Influenza Virus Resource Database, representing the spectrum of H9N2 influenza viruses isolated from 1966 to 2009. Our study provides a panoramic framework for better understanding the genesis and evolution of H9N2 influenza viruses, and for describing the history of H9N2 viruses circulating in diverse hosts. Panorama phylogenetic analysis of the eight viral gene segments revealed the complexity and diversity of H9N2 influenza viruses. The 571 H9N2 viral genomes were classified into 74 separate lineages, which had marked host and geographical differences in phylogeny. Panorama genotypical analysis also revealed that H9N2 viruses include at least 98 genotypes, which were further divided according to their HA lineages into seven series (A–G). Phylogenetic analysis of the internal genes showed that H9N2 viruses are closely related to H3, H4, H5, H7, H10, and H14 subtype influenza viruses. Our results indicate that H9N2 viruses have undergone extensive reassortments to generate multiple reassortants and genotypes, suggesting that the continued circulation of multiple genotypical H9N2 viruses throughout the world in diverse hosts has the potential to cause future influenza outbreaks in poultry and epidemics in humans. We propose a nomenclature system for identifying and unifying all lineages and genotypes of H9N2 influenza viruses in order to facilitate international communication on the evolution, ecology and epidemiology of H9N2 influenza viruses.

Highlights

Sixteen HA and nine NA subtype influenza A viruses have been detected in poultry and wild birds around the world [1]
Recent studies have shown that H9N2 viruses may have contributed to the genetic and geographic diversity of H5N1 viruses [5,17], such as the 1997 Hong Kong H5N1 influenza viruses which had internal genes probably derived from the isolate A/Quail/HongKong/G1/97(H9N2) [5,18]
These findings suggest that continuous circulation of H9N2 influenza viruses among different hosts has the potential to cause outbreaks in poultry and epidemics in humans

Summary

Introduction

Sixteen HA and nine NA subtype influenza A viruses have been detected in poultry and wild birds around the world [1]. H9 subtype viruses generally exist as low pathogenicity influenza viruses causing mild to moderate disease They have been associated with severe morbidity and mortality in poultry as a result of co-infection with other pathogens [6,7]. Recent studies have shown that H9N2 viruses may have contributed to the genetic and geographic diversity of H5N1 viruses [5,17], such as the 1997 Hong Kong H5N1 influenza viruses which had internal genes probably derived from the isolate A/Quail/HongKong/G1/97(H9N2) [5,18] These findings suggest that continuous circulation of H9N2 influenza viruses among different hosts has the potential to cause outbreaks in poultry and epidemics in humans. We provide a framework for obtaining a panoramic understanding of H9N2 viral evolution and propose a precise nomenclature system for unifying all lineages and genotypes of H9N2 influenza viruses in order to improve our ability to predict the direction of evolution by monitoring changes in the viral genome

Results

Discussion

Methods