Abstract

H9N2 subtype avian influenza virus (AIV) is widely prevalent in poultry, and the virus is becoming adaptive to mammals, which poses pandemic importance. Here, BALB/c mice were employed as a model to evaluate the adaption in mammals of 21 field H9N2 viruses isolated from avian species between 2016 to 2019 in China. The replication capacity of the viruses was evaluated in the lungs of mice. The pathogenicity of the viruses were compared by weight loss and lung lesions from infected mice. The whole genomic sequences of the viruses were further characterized to define the associated phenotypes of the H9N2 viruses in vitro and in vivo. The results showed that most viruses could replicate well and cause lesions in the mouse lungs. The propagation capacity in MDCK cells and damage to respiratory tissues of the infected mice corresponded to relative viral titers in the mouse lungs. Further genome analysis showed that all of the H9N2 viruses belonged to the same genotype, G57, and contained a couple of amino acid substitutions or deletions that have been demonstrated as avian-human markers. Additionally, nine amino acids residues in seven viral proteins were found to be correlated with the replication phenotypes of the H9N2 viruses in mammals. The study demonstrated that a well-defined H9N2 AIV genotype with high adaption in mammals was prevalent in China in recent years. Further investigations on the role of the identified residues and continuous surveillance of newly identified mutations associated with host adaption should be strengthened to prevent any devastating human influenza pandemics.

Highlights

  • H9N2 influenza viruses were first isolated from turkeys in North America in 1966 [1]

  • H9N2 subtype avian influenza virus (AIV) is widely prevalent in poultry, and the virus is becoming adaptive to mammals [7,9,10]

  • We used BALB/c mice as a model to evaluate the replication capacity in mammalian hosts of the field H9N2 viruses isolated from avian species in China

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Summary

Introduction

H9N2 influenza viruses were first isolated from turkeys in North America in 1966 [1]. Infections of H9N2 avian influenza virus (AIV) strains in domestic poultry in Mainland China became established during the mid-1990s, and have become the most prevalent subtype of influenza viruses in multiple avian species [2,3,4]. Viruses 2020, 12, 432 populations in Asia occasionally transmit to humans and mammals [6,7]. H9N2 subtype viruses were isolated from pigs in 1998 [8] and, subsequently, were isolated from humans with influenza-like illness in Hong Kong and Mainland China [9,10]. The possession of human-like receptor specificity and occasional transmission of H9N2 AIV to mammalian species raise public concerns on the potential threat of this virus in humans [7,11,12,13,14]. H9N2 AIVs are considered as significant donors contributing to the emergence of a novel subtype of AIV that has human health implications [15]

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