New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five
文献类型： 外文期刊
作者： Quan, Chuansong 1 ; Shi, Weifeng 3 ; Yang, Yang 4 ; Yang, Yongchun 5 ; Liu, Xiaoqing 6 ; Xu, Wen 7 ; Li, Hong 7 ; Li, Jua 1 ;
作者机构： 1.Chinese Ctr Dis Control & Prevent China CDC, Natl Inst Viral Dis Control & Prevent, Beijing, Peoples R China
2.Chinese Acad Sci, CAS Key Lab Pathogen Microbiol & Immunol, Collaborat Innovat Ctr Diag & Treatment Infect Di, Inst Microbiol,Ctr Influenza Res & Early Warning, Beijing, Peoples R China
3.Taishan Med Coll, Key Lab Etiol & Epidemiol Emerging Infect Dis Uni, Tai An, Shandong, Peoples R China
4.Shenzhen Third Peoples Hosp, Shenzhen Key Lab Pathogen & Immun, State Key Discipline Infect Dis, Shenzhen, Peoples R China
5.Zhejiang Agr & Forestry Univ, Coll Anim Sci & Technol, Ctr Excellence Anim Hlth Inspect, Hangzhou, Zhejiang, Peoples R China
6.Jiangxi Prov Ctr Dis Control & Prevent, Nanchang, Jiangxi, Peoples R China
7.Yunnan Ctr Dis Control & Prevent, Kunming, Yunnan, Peoples R China
8.Fudan Univ, Key Lab Publ Hlth Safety, Sch Publ Hlth, Minist Educ, Shanghai, Peoples R China
9.Xinjiang Univ, Coll Life Sci & Technol, Urumqi, Peoples R China
10.Fujian Acad Agr Sci, Inst Anim Husb & Vet Med, Fuzhou, Fujian, Peoples R China
11.Dongguan Municipal Ctr Dis Control & Prevent, Dongguan, Peoples R China
关键词： H7N9; HPAIV; wave five; avian influenza virus; dynamic reassortment; evolution; genetic diversity; origin
期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.103； 五年影响因子：5.078 ）
ISSN： 0022-538X
年卷期： 2018 年 92 卷 11 期
页码：
收录情况： SCI
摘要： H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in wave 5; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny, and genetic evolution of 240 H7N9 viruses in wave 5, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis indicated that the newly emerging highly pathogenic (HP) and low-pathogenicity (LP) H7N9 viruses were cocirculating, causing human and poultry infections across China. Genetic analysis indicated that dynamic reassortment of the internal genes among LP-H7N9/H9N2/H6Ny and HP-H7N9, as well as of the surface genes, between the Yangtze and Pearl River Delta lineages resulted in at least 36 genotypes, with three major genotypes (G1 [A/chicken/Jiangsu/SC537/2013-like], G3 [A/Chicken/Zhongshan/ZS/2017-like], and G11 [A/Anhui/40094/2015-like]). The HP-H7N9 genotype likely evolved from G1 LP-H7N9 by the insertion of a KRTA motif at the cleavage site (CS) and then evolved into 15 genotypes with four different CS motifs, including PKGKRTAR/G, PKGKRIAR/G, PKRKRAAR/G, and PKRKRTAR/G. Approximately 46% (28/61) of HP strains belonged to G3. Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains. In summary, the enhanced prevalence and diverse genetic characteristics that occurred with mammalian-adapted and NAI-resistant mutations may have contributed to increased numbers of human infections in wave 5. IMPORTANCE The highest numbers of human H7N9 infections were observed during wave 5 from October 2016 to September 2017. Our results showed that HP-H7N9 and LP-H7N9 had spread virtually throughout China and underwent dynamic reassortment with different subtypes (H7N9/H9N2 and H6Ny) and lineages (Yangtze and Pearl River Delta lineages), resulting in totals of 36 and 3 major genotypes, respectively. Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections. The broad dissemination of LP-and HP-H7N9 with high levels of genetic diversity and host adaptation and drug-resistant mutations likely accounted for the sharp increases in the number of human infections during wave 5. Therefore, more strategies are needed against the further spread and damage of H7N9 in the world.
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