机构：[a]National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention(China CDC), Beijing, China[b]CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center forDiagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research andEarly-Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China[c]Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong,Taishan Medical College, Taian, China[d]Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, ShenzhenThird People's Hospital, Shenzhen, China[e]Center of Excellence for Animal Health Inspection, College of Animal Science and Technology, ZhejiangAgriculture and Forestry University, Hangzhou, China[f]Jiangxi Province Center for Disease Control and Prevention, Nanchang, China[g]Yunnan Center for Disease Control and Prevention, Kunming, China[h]School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education,Shanghai, China[i]College of Life Science and Technology, Xinjiang University, Urumchi, China[j]Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou,China[k]Dongguan Municipal Center for Disease Control and Prevention, Dongguan, China
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.
基金：
National Key Research and Development Project of China [2016YFE0205800]; National Science and Technology Major Project [2016ZX10004222, 2018ZX10713001-010]; Ministry of Science and Technology of China (MOST) 973 Project [2015CB910501]; Chinese Academy of SciencesChinese Academy of Sciences [KJZD-EW-L15]; Sanming Project of Medicine in Shenzhen [ZDSYS201504301534057]; Shenzhen Science and Technology Research and Development Project [JCYJ20160427151920801, JCYJ20151029151932602]; National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China [81470096]; Science Foundation of Two Sides of Strait [U1305212]; External Cooperation Program of Chinese Academy of SciencesChinese Academy of Sciences [153211KYSB20160001]; Taishan Scholars program of Shandong Province [ts201511056]; Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS) [2017122]
第一作者机构：[a]National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention(China CDC), Beijing, China[b]CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center forDiagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research andEarly-Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[a]National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention(China CDC), Beijing, China[b]CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center forDiagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research andEarly-Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China[d]Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, ShenzhenThird People's Hospital, Shenzhen, China
推荐引用方式(GB/T 7714)：
Chuansong Quan,Weifeng Shi,Yang Yang,et al.New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five[J].JOURNAL OF VIROLOGY.2018,92(11):doi:10.1128/JVI.00301-18.
APA：
Chuansong Quan,Weifeng Shi,Yang Yang,Yongchun Yang,Xiaoqing Liu...&Yuhai Bi.(2018).New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five.JOURNAL OF VIROLOGY,92,(11)
MLA：
Chuansong Quan,et al."New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five".JOURNAL OF VIROLOGY 92..11(2018)
医学