Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China.

Xin Yin,Jianzhong Shi,Liling Liu,Yan Chen,Xiurong Wang,Yaping Zhang,Pengfei Cui,Yanjing Liu,Xianying Zeng,Yanbing Li,Yuntao Guan,Hualan Chen,Dongxue Wang,Guohua Deng,Shuxin Pan,Guobin Tian,Yasuo Suzuki,Xiaohan Chen,Yujie Hou,J Fang ,Chengjun Liu

doi:10.1371/journal.ppat.1009561

Xin Yin, Jianzhong Shi + Show 19 more

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https://doi.org/10.1371/journal.ppat.1009561

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Abstract

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control.

Highlights

H7N9 influenza viruses emerged in China in early 2013 and caused five waves of human infections from 2013–2017, with a total of 1568 cases, of which 615 were fatal [1]
Human infection with H7N9 virus has been successfully prevented since the application of an H7N9 vaccine in poultry in September 2017 in China; the H7N9 virus has not been eradicated from poultry
We evaluated the genetic and biologic properties of H7N9 viruses detected in poultry in China from February 2018 to December 2019

Summary

Introduction

H7N9 influenza viruses emerged in China in early 2013 and caused five waves of human infections from 2013–2017, with a total of 1568 cases, of which 615 were fatal [1]. After four years of circulation in nature, some low pathogenic H7N9 strains acquired an insertion of four amino acids in their hemagglutinin (HA) cleavage site in early 2017 and became highly pathogenic in chickens, causing severe influenza outbreaks in poultry in China [5,6,7]. These highly pathogenic H7N9 viruses posed an increased threat to human health given their pandemic potential and virulence to humans [7,8,9]. The vaccination of chickens successfully prevented human infections with H7N9 virus as indicated by the fact that there were 766 human cases reported between October 1, 2016, and September 30, 2017, but only three and one human case over the same time period of the following two years [13, 14], and no human case has been detected since March 2019 [1, 15] (S1 Fig)

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