What happened during the fifth wave of H7N9 epidemic: LPAI and HPAI H7N9 viruses
Wenfei Zhu1, Lei Yang1, Dayan Wang1 Yuelong Shu1,2
1National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention; Beijing 102206, P.R. China; 2School of Public Health (Shenzhen), Sun Yat-sen University, Guangdong, 510275, P.R. China
Since the emergence of a novel avian influenza A H7N9 virus in the Yangtze Delta Region in spring 2013, human cases infected with H7N9 viruses have occurred every winter-spring season in Mainland China. The fifth epidemic wave during 2016-2017 winter-spring season was the largest one to date. This situation prompted concern that a genetic change may underlie increased virulence. Based on an evolutionary analysis of H7N9 viruses from all five outbreak waves, we find that additional subclades of the H7 and N9 genes have emerged. Our analysis indicates that H7N9 viruses inherited NP genes from co-circulating H7N9 instead of H9N2 viruses. Genotypic diversity among H7N9 viruses increased following wave I, peaked during wave III, and rapidly deceased thereafter with minimal diversity in wave V, suggesting that the viruses entered a relatively stable evolutionary stage. The ZJ11 genotype caused the majority of human infections in wave V. We suggest that the largest outbreak of wave V may be due to a constellation of genes rather than a single mutation.
During the wave V, highly pathogenic variants of these H7N9 viruses (HPAI H7N9) have emerged and caused human infections and poultry outbreaks in Mainland China. The HPAI H7N9) virus contained a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Although maintaining dual receptor-binding preference, its HA antigenicity was distinct from low-pathogenic avian influenza A (H7N9). How the HPAI H7N9 virus was generated and how it evolved and spread in China are important for outbreak control and prevention. Here, we show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze Delta Region and spread southward to the Pearl Delta Region, possibly through live poultry trades. After introduction into the Pearl Delta Region, the origin LPAI H7N9 virus acquired four amino acid insertions in the HA protein cleavage site and mutated into the HPAI H7N9 virus in late May 2016. Afterward, the HPAI H7N9 viruses further reassorted with LPAI H7N9 or H9N2 viruses locally and generated multiple different genotypes. The rapid geographical expansion and genetic evolution of the LPAI and HPAI H7N9 viruses pose a great challenge, not only to public health, but also to poultry production. Effective control measures, including enhanced surveillance, are therefore urgently needed.