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

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.

A Single Mutation at Position 190 in Hemagglutinin Enhances Binding Affinity for Human Type Sialic Acid Receptor and Replication of H9N2 Avian Influenza Virus in Mice

“…Virus genotype was defined based on gene phylogenic analysis. The H9N2 viruses harboring G1-like genes were designated the genotype A series, while viruses harboring Ck/BJ/94-like genes were designated the genotype B series and further delineated as genotypes B1 to B65 as described previously (33)(34)(35)(36). The analyzed sequences were derived from viruses isolated in this study or were downloaded from GenBank.…”

Molecular Identification of Pre-Existing Immunityin Human against H9N2 Influenza Viruses Using HLA-A*0201 Binding Peptides

“…During the last two decades, several distinct lineages and sublineages of H9N2 viruses have become established and the viruses classified in at least seven genotypes series A-G. Among them G1-like viruses (genotypes A1-A3, A5, and A9) have been dominated in Middle east whereas, the genotypic complexity of the viruses shown in China (27,28 (18,28). It is expected that the region has not been exposed by novel genotype.…”

Isolation and phylogenetic characterization of haemagglutinin and neuraminidase genes of H9N2 low pathogenicity avian influenza virus isolated from commercial layers in India

“…In poultry, two types of AIV have been described based on their pathogenicity, namely, a highly pathogenic type (HPAIV) that causes severe disease with high mortality and a low pathogenic type (LPAIV) that causes only asymptomatic infection or a mild disease [4]. Since the first detection from turkeys in Wisconsin in 1966 [5][6][7], the LPAI H9N2 virus subtype has widely circulated. In Asia, H9N2 viruses were regularly isolated from ducks [8][9][10].…”