Reassortment and adaptive mutations of an emerging avian influenza virus H7N4 subtype in China.

Bingqian Qu,Carol J Cardona,Xue Li,Zheng Xing

doi:10.1371/journal.pone.0227597

Bingqian Qu, Carol J Cardona + Show 2 more

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https://doi.org/10.1371/journal.pone.0227597

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Journal: PloS one	Publication Date: Jan 17, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: University of Minnesota, Nanjing University

Abstract

Human infections with avian influenza viruses including H5, H7 and H9 hemagglutinin subtypes occur at a low rate. Among human infections with H7 viruses, regional outbreaks with H7N2, H7N3, H7N7 and H7N9 have been documented. Early in 2018, a human infection with a novel H7N4 avian influenza virus was reported in Jiangsu, China. This study is aimed at understanding the probable origin and molecular features of this emerging H7N4 virus. Genomic segments encoding hemagglutinin (HA) and neuraminidase (NA) of H7Nx and HxN4 viruses were compared with this H7N4 strain by alignment and phylogenetic tree analysis. Phylogenetic analysis indicated that the human H7N4 virus probably originated from multiple reassortments of avian H7N7 and H8N4 viruses for its HA and NA, respectively, and likely a regional uncharacterized virus for its internal segments. Our data excluded that circulating avian H9N2 viruses were the origin of the H7N4 internal segments, unlike the human H5N1 and H7N9 viruses that both had H9N2 backbones. This index case provided a unique opportunity to examine viral mutations by directly comparing the human isolate with its closest viral relatives isolated from avian species from the patient’s farm, which may suggest critical mutations required for viral adaptation in humans. Whole-genome scanning was performed and the sequences of the human and related avian H7N4 isolates were compared. Mutations in PB2 (E627K), PB2 (K683T), PB1-F2 (N47S), HA (N283D), HA(K321E), NA(A137V), NA(K296R) and M2 (C19Y) were identified in the human isolate while no mutations were found in PB1, NP, NS1, and NS2 of the human H7N4 compared to the avian H7N4 viruses. Our data in this report provide further evidence for the genesis of this novel H7N4 virus with a multi-reassortment model and show molecular changes that might be responsible for the transmission of this virus from chickens or ducks to and subsequent replication in humans.

Highlights

Influenza A virus is classified into 18 hemagglutinin (HA) and 11 neuraminidase (NA) subtypes [1]
Six internal genomic segments of the human H7N4 virus were derived from H7N7, H8N4 and H5N1 but not circulating H9N2 viruses
Our data showed that the HA and NA genomes of a novel human H7N4 isolate were not homologous to those of previously published H7N4 viral sequences, but closer to the HA of an H7N7 and the NA of an H8N4 avian influenza viruses (AIV) from two distant and different geographic regions, indicating a probable reassortment (Figs 1 & 3)

Summary

Introduction

Influenza A virus is classified into 18 hemagglutinin (HA) and 11 neuraminidase (NA) subtypes [1]. Human infections with avian influenza viruses (AIV) do occur, albeit at a very low rate. Some avian viruses, including H5 or H7 subtypes, have crossed species barriers with acquired ability from mutations and caused sporadic infections or regional and even intercontinental outbreaks in humans with high pathogenicity and fatality rates [2]. Among human infections with H7 viruses, geographical distribution showed that infections with H7N2 (New York) and H7N3 (Canada, Mexico) were the only documented cases in Northern America, whereas H7N7 outbreaks occurred in England, the Netherlands, and Italy [3]. Human infections with a novel H7N9 virus was first reported in China, 2013, and has since become a severe public health threat with high mortality rates. Other H7 subtype viruses have not been detected in humans

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