Continual Antigenic Diversification in China Leads to Global Antigenic Complexity of Avian Influenza H5N1 Viruses

Yousong Peng,Hong Bo,Ye Zhang,Yuelong Shu,Dayan Wang,Xiaodan Li,Meilin Jin,Hongbo Zhou,Aiping Wu,Rongbao Gao,Taijiao Jiang,Xian Lin,Lei Yang,Libo Dong

doi:10.1038/srep43566

Abstract

The highly pathogenic avian influenza (HPAI) H5N1 virus poses a significant potential threat to human society due to its wide spread and rapid evolution. In this study, we present a comprehensive antigenic map for HPAI H5N1 viruses including 218 newly sequenced isolates from diverse regions of mainland China, by computationally separating almost all HPAI H5N1 viruses into 15 major antigenic clusters (ACs) based on their hemagglutinin sequences. Phylogenetic analysis showed that 12 of these 15 ACs originated in China in a divergent pattern. Further analysis of the dissemination of HPAI H5N1 virus in China identified that the virus’s geographic expansion was co-incident with a significant divergence in antigenicity. Moreover, this antigenic diversification leads to global antigenic complexity, as typified by the recent HPAI H5N1 spread, showing extensive co-circulation and local persistence. This analysis has highlighted the challenge in H5N1 prevention and control that requires different planning strategies even inside China.

Highlights

The highly pathogenic avian influenza (HPAI) H5N1 virus has become of global concern since the isolation and identification of the strain A/Goose/Guangdong/1/1996 (GsGD) in Guangdong province of China in 19961–3
Important to note is that, except for Hainan, Jiangsu, Shanghai and Yunnan, the sampling covered all provinces of southern China, a region supposed to be the epicenter of the HPAI H5N1 virus[15,28,29]
In this study antigenic modeling was performed, based on existing HA1 sequences of HPAI H5N1 viruses and supplemented with 218 newly sequenced strains isolated during 2004–2013 from mainland China. This analysis provides a comprehensive picture of the antigenic evolution of HPAI H5N1 virus across the globe

Summary

Introduction

The highly pathogenic avian influenza (HPAI) H5N1 virus has become of global concern since the isolation and identification of the strain A/Goose/Guangdong/1/1996 (GsGD) in Guangdong province of China in 19961–3. For ease of tracking the evolution of the virus, the H5N1 Evolution Working Group (HEWG), a joint effort of the World Health Organization (WHO), World Organisation for Animal Health (OIE) and Food and Agriculture Organization (FAO), has designed a nomenclature to classify the GsGD lineage of Eurasian HPAI H5N1 viruses[24,25], based on the phylogeny of the antigen hemagglutinin (HA). According to this nomenclature, all viruses of the GsGD lineage are classified into 10 clades (numbered 0 to 9), which are further subdivided into second-order, third-order and even fourth-order subclades. Through accurate modeling of these newly sequenced virus and viruses with HA gene sequences available from public databases, we developed a comprehensive picture of the antigenic evolution of HPAI H5N1 viruses across the globe

Methods

Results

Conclusion