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Science China(Life Sciences) 2019年第1期62卷 76-83页

作者： Chunyang Gu Xianying Zeng Yangming Song Yanbing Li liling liu Yoshihiro Kawaoka Dongming Zhao Hualan Chen State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Division of Virology Department of Microbiology and Immunology Institute of Medical Science University of Tokyo

Antigenic drift forces us to frequently update influenza vaccines; however, the genetic basis for antigenic variation remains largely unknown. In this study, we used clade 7.2 H5 viruses as models to explore the molecular determinants of influenza virus antigenic variation. We generated eight monoclonal antibodies(MAbs) targeted to the hemagglutinin(HA) protein of the index virus A/chicken/Shanxi/2/2006 and found that two representative antigenically drifted clade 7.2 viruses did not react with six of the eight MAbs. The E131 N mutation and insertion of leucine at position 134 in the HA protein of the antigenically drifted strains eliminated the reactivity of the virus with the MAbs. We also found that the amino acid N131 in the H5 HA protein is glycosylated. Our results provide experimental evidence that glycosylation and an amino acid insertion or deletion in HA influence antigenic variation.

关键词： Influenza virus H5N1 antigenic variation genetic basis

Analysis on Economic Resilience of the Guangdong-Hong Kong-Macao Greater Bay Area:A Perspective from the Economic Connection Network

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China Economic Transition 2023年第3期6卷 355-374页

作者： QIN Chenglin liu liling School of Economics Jinan UniversityGuangzhou 510632China

In the face of an increasingly complex and unstable external development environment,enhancing economic resilience has become a key task in the construction of the Guangdong-Hong Kong-Macao Greater Bay *** paper analyzes the changes in the economic resilience of the Guangdong-Hong Kong-Macao Greater Bay Area and its constituent cities after the 2008 global financial crisis by virtue of the regional economic resilience assessment method proposed by Martin et *** constructs an economic connection network for the Guangdong-Hong Kong-Macao Greater Bay Area using the data from corporate headquarters and branches of A-share listed companies to analyze its impact on the economic resilience of the *** study reveals the three following ***,the economic resilience of the Guangdong-Hong Kong-Macao Greater Bay Area generally outperforms the national average level,seeing a rapid boost over the recent years and exceeding the level witnessed during the 2008 financial ***,there are marked disparities in the economic resilience ofvarious cities within the Greater Bay Area,with Shenzhen,Guangzhou,and Dongguan emerging as the most robust in this ***,the economic connection network has a positive impact on the economic resilience of the cities in the Guangdong-Hong Kong-Macao Greater Bay ***,there is a positive correlation between a city's economic resilience and its centrality in the economic *** exerts a positive spillover effect on the economic resilience of surrounding ***,from the perspective of industryspecific networks,circulation and service industry networks are more conducive to improving the economic resilience of a *** the significant role of the economic connection network in shaping regional and urban economic resilience,it is imperative for the Guangdong-Hong Kong-Macao Greater Bay Area to prioritize ensuring economic development security and enhancing economi

关键词： economic resilience economic connection network network centrality Guangdong-Hongg Kong-MacaoGreater Bay Area

Continued evolution of the Eurasian avian-like H1N1 swine influenza viruses in China

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Science China(Life Sciences) 2023年第2期66卷 269-282页

作者： Fei Meng Yan Chen Zuchen Song Qiu Zhong Yijie Zhang Chuanling Qiao Cheng Yan Huihui Kong liling liu Chengjun Li Huanliang Yang Hualan Chen State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Animal influenza viruses continue to pose a threat to human public health. The Eurasian avian-like H1N1(EA H1N1) viruses are widespread in pigs throughout Europe and China and have caused human infections in several countries, indicating their pandemic potential. To carefully monitor the evolution of the EA H1N1 viruses in nature, we collected nasal swabs from 103,110pigs in 22 provinces in China between October 2013 and December 2019, and isolated 855 EA H1N1 viruses. Genomic analysis of 319 representative viruses revealed that these EA H1N1 viruses formed eight different genotypes through reassortment with viruses of other lineages circulating in humans and pigs, and two of these genotypes(G4 and G5) were widely distributed in *** studies indicated that some strains have become highly pathogenic in mice and highly transmissible in ferrets via respiratory droplets. Moreover, two-thirds of the EA H1N1 viruses reacted poorly with ferret serum antibodies induced by the currently used H1N1 human influenza vaccine, suggesting that existing immunity may not prevent the transmission of the EA H1N1 viruses in humans. Our study reveals the evolution and pandemic potential of EA H1N1 viruses and provides important insights for future pandemic preparedness.

关键词： H1N1 influenza immunity

Isolation and characterization of H7N9 viruses from live poultry markets--Implication of the source of current H7N9 infection in humans

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Chinese Science Bulletin 2013年第16期58卷 1857-1863页

作者： SHI JianZhong DENG GuoHua liu PeiHong ZHOU JinPing GUAN LiZheng LI WenHui LI XuYong GUO Jing WANG GuoJun FAN Jun WANG JinLiang LI YuanYuan JIANG YongPing liu liling TIAN GuoBin LI ChengJun CHEN HuaLan Animal Influenza Laboratory State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Shanghai Animal Disease Control Center

On March 31, 2013, the National Health and Family Planning Commission announced that human infections with a previously undescribed influenza A (H7N9) virus had occurred in Shanghai and Anhui Province, China. To investigate the possible origins of the H7N9 viruses causing these human infections, we collected 970 samples, including drinking water, soil, and cloacal and tracheal swabs of poultry from live poultry markets and poultry farms in Shanghai and Anhui Province. Twenty samples were positive for the H7N9 influenza virus. Notably, all 20 viruses were isolated from samples collected from live poultry markets in Shanghai. Phylogenetic analyses showed that the six internal genes of these novel human H7N9 viruses were derived from avian H9N2 viruses, but the ancestor of their HA and NA genes is uncertain. When we examined the phylogenetic relationship between the H7N9 isolates from live poultry markets and the viruses that caused the human infections, we found that they shared high homology across all eight gene segments. We thus identified the direct avian origin of the H7N9 influenza viruses that caused the human infections. Importantly, we observed that the H7N9 viruses isolated from humans had acquired critical mutations that made them more "human-like". It is therefore imperative to take strong measures to control the spread of H7N9 viruses in birds and humans to prevent further threats to human health.

关键词：流感病毒人类感染市场活禽分离感染源鉴定蕴涵

M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

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Science China(Life Sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng liling liu Hualan Chen Chengjun Li State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

Influenza A virus use of BinCARD1 to facilitate the binding of viral NP to importinα7 is counteracted by TBK1-p62 axis-mediated autophagy

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Cellular & Molecular Immunology 2022年第10期19卷 1168-1184页

作者： Xuyuan Wang Li Jiang Guangwen Wang Wenjun Shi Yuzhen Hu Bo Wang Xianying Zeng Guobin Tian Guohua Deng Jianzhong Shi liling liu Chengjun Li Hualan Chen College of Veterinary Medicine Gansu Agricultural UniversityLanzhou730070China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou510642China State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin150069China

As a major component of the viral ribonucleoprotein(vRNP)complex in influenza A virus(IAV),nucleoprotein(NP)interacts with isoforms of importinαfamily members,leading to the import of itself and vRNP complex into the nucleus,a process pivotal in the replication cycle of *** this study,we found that BinCARD1,an isoform of Bcl10-interacting protein with CARD(BinCARD),was leveraged by IAV for efficient viral ***1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex ***,we found that BinCARD1 interacted with NP to promote NP binding to importinα7,an adaptor in the host nuclear import ***,we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3,and that TBK1 appeared to degrade *** showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage,which was recognized by the TBK1-p62 axis for autophagic ***,our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication,and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.

关键词： Influenza A virus BinCARD1 TRAF3 TBK1 p62

TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

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Protein & Cell 2020年第12期11卷 894-914页

作者： Nan Sun Li Jiang Miaomiao Ye Yihan Wang Guangwen Wang Xiaopeng Wan Yuhui Zhao Xia Wen Libin Liang Shujie Ma liling liu Zhigao Bu Hualan Chen Chengjun Li State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Tripartite motif(TRIM)family proteins are important effectors of innate immunity against viral *** we identified TRIM35 as a regulator of TRAF3 *** in or inhibition of TRIM35 suppressed the production of type I interferon(IFN)in response to viral infection.777m35-deficient mice were more susceptible to influenza A virus(IAV)infection than were wild-type ***35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and *** PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of ***35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2,thereby antagonizing its suppression of TRAF3 *** in vitro and in vivo findings thus reveal novel roles of TRIM35,through catalyzing Lys63-or Lys48-linked polyubiquitination,in RIG-I antiviral immunity and mechanism of defense against IAV infection.

关键词： influenza A virus PB2 TRIM35 TRAF3 ubiquitination antiviral immunity

教育政策、课程与全球化——访美国威斯康星大学阿普尔教授

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全球教育展望 2007年第3期36卷 3-8页

作者：刘丽玲首都经济贸易大学劳动经济学院副教授北京100026

迈克尔·阿普尔(Michael Apple)系美国威斯康星大学教授,国际著名课程与教育政策研究专家。《意识形态与课程》、《教师与文本》等著作的作者。本访谈最早完成于2002年7月在北京召开的全球学习大会上,后来作者在伦敦做博士后期间以及阿... 详细信息

迈克尔·阿普尔(Michael Apple)系美国威斯康星大学教授,国际著名课程与教育政策研究专家。《意识形态与课程》、《教师与文本》等著作的作者。本访谈最早完成于2002年7月在北京召开的全球学习大会上,后来作者在伦敦做博士后期间以及阿普尔2006年3月来北京参加国际会议期间,又与阿普尔教授有交流,有些内容曾经有过修改和补充。

关键词：威斯康星大学教育政策研究阿普尔课程美国全球化国际会议大学教授

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嵌入批判思维的领导力开发

中国人力资源开发 2009年第7期26卷 41-44页

作者：刘丽玲首都经济贸易大学

本文阐述了批判思维的概念和主要特点,介绍了以提高批判思维为核心的领导力开发模型,并依据该模型说明了不同阶段的培训课程体系设计及其效果评估。

关键词：批判思维领导力开发领导力开发模型

Genetic and biological characteristics of the globally circulating H5N8 avian influenza viruses and the protective efficacy offered by the poultry vaccine currently used in China

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Science China(Life Sciences) 2022年第4期65卷 795-808页

作者： Pengfei Cui Xianying Zeng Xuyong Li Yanbing Li Jianzhong Shi Conghui Zhao Zhiyuan Qu Yanwen Wang Jing Guo Wenli Gu Qi Ma Yuancheng Zhang Weipeng Lin Minghui Li Jingman Tian Dongxue Wang Xin Xing Yanjing liu Shuxin Pan Yaping Zhang Hongmei Bao liling liu Guobin Tian Chengjun Li Guohua Deng Hualan Chen State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin150069China College of Agronomy Liaocheng UniversityLiaocheng252000China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou510642China

The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor the invasion and spread of the H5N8 virus in China, we performed active surveillance by analyzing 317 wild bird samples and swab samples collected from 41,172 poultry all over the country. We isolated 22 H5N8 viruses from wild birds and 14 H5N8 viruses from waterfowls. Genetic analysis indicated that the 36 viruses formed two different genotypes: one genotype viruses were widely detected from different wild birds and domestic waterfowls;the other genotype was isolated from a whopper swan. We further revealed the origin and spatiotemporal spread of these two distinct H5N8 virus genotypes in 2020 and 2021. Animal studies indicated that the H5N8 isolates are highly pathogenic to chickens, mildly pathogenic in ducks, but have distinct pathotypes in mice. Moreover, we found that vaccinated poultry in China could be completely protected against H5N8 virus challenge. Given that the H5N8 viruses are likely to continue to spread in wild birds, vaccination of poultry is highly recommended in high-risk countries to prevent H5N8 avian influenza.

关键词： avian influenza virus H5N8 evolution pathogenicity antigenicity vaccine protective efficacy