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Control of highly pathogenic avian influenza through vaccination

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Journal of Integrative Agriculture 2024年第5期23卷 1447-1453页

作者： Xianying Zeng Jianzhong Shi hualan chen State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin150069China

The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to *** this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and *** addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.

关键词： avian influenza control highly pathogenic vaccination

Vaccination of poultry successfully eliminated human infection with H7N9 virus in China

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Science China(Life Sciences) 2018年第12期61卷 1465-1473页

作者： Xianying Zeng Guobin Tian Jianzhong Shi Guohua Deng chengjun Li hualan chen State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

The H7 N9 viruses that emerged in China in 2013 were nonpathogenic in chickens but mutated to a highly pathogenic form in early 2017 and caused severe disease outbreaks in chickens. The H7 N9 influenza viruses have caused five waves of human infection, with almost half of the total number of human cases(766 of 1,567) being reported in the fifth wave, raising concerns that even more human infections could occur in the sixth wave. In September 2017, an H5/H7 bivalent inactivated vaccine for chickens was introduced, and the H7 N9 virus isolation rate in poultry dropped by 93.3% after vaccination. More importantly,only three H7 N9 human cases were reported between October 1, 2017 and September 30, 2018, indicating that vaccination of poultry successfully eliminated human infection with H7 N9 virus. These facts emphasize that active control of animal disease is extremely important for zoonosis control and human health protection.

关键词： H7N9 influenza virus evolution vaccination human infection elimination

Glycosylation and an amino acid insertion in the head of hemagglutinin independently affect the antigenic properties of H5N1 avian influenza viruses

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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

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

Inactivated H9N2 vaccines developed with early strains do not protect against recent H9N2 viruses:Call for a change in H9N2 control policy

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Journal of Integrative Agriculture 2024年第6期23卷 2144-2148页

作者： Yanjing Liu Qingqing Yu Xiangyu Zhou Wenxin Li Xinwen He Yan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng hualan chen College of Veterinary Medicine Gansu Agricultural UniversityLanzhou 730070China State Key Laboratory for Animal Disease Control and Prevention Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry DiseasesMinistry of Agriculture and Rural Affairs/Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150009China National Poultry Laboratory Animal Resource Center Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150009China Harbin Weike Biotechnology Co. Ltd.Harbin 150009China

H9N2 virus has been widely distributed in wild birds and poultry around the world since its first emergence in the United States of America in 1966(Gu et al.2017;Carnaccini and Perez 2020).The virus appeared in chickens in China in the early 1990s,and over the last two decades has gradually become the dominant epidemic subtype(Sun and Liu 2015;Bi et al.2020).Although H9N2 virus infection alone cannot cause severe disease or death in poultry,H9N2 virus-infected birds experience a degree of egg production drop and can be easily infected by other pathogens,thus causing economic losses for poultry industry.

关键词： H9N2 poultry policy

Prevalence,genetics,Virulence,and transmissibility of H7N9 influenza viruses

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Prevalence,genetics,Virulence,and transmissibility of H7N9 i...

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

第十二届全国免疫学学术大会

作者： hualan chen National Avian influenza Reference Laboratory Harbin veterinary Research institute Chinese Academy of Agricultural Sciences

In February 2013,newly emerged H7N9 avian influenza viruses caused human infections in Shanghai and Anhui *** efforts to control them,H7N9 influenza viruses continue to evolve and *** of 13 August2017,H7N9 viruses had caused 1560 human infections and 609 *** replication in humans,H7N9 influenza viruses can obtain mutations that increase their virulence and transmissibility in *** the H7N9 viruses isolated from birds are nonlethal in chickens,which allows them to replicate silently and acquire

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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

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

H7N9 virus infection triggers lethal cytokine storm by activating gasdermin E-mediated pyroptosis of lung alveolar epithelial cells

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National Science Review 2022年第1期9卷 47-55页

作者： Xiaopeng Wan Jiqing Li Yupeng Wang Xiaofei Yu Xijun He Jianzhong Shi Guohua Deng Xianying Zeng Guobin Tian Yanbing Li Yongping Jiang Yuntao Guan chengjun Li Feng Shao hualan chen State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences National Institute of Biological Sciences

The H7 N9 influenza virus emerged in China in 2013,causing more than 1560 human infections,39% of which were fatal.A ’cytokine storm’ in the lungs of H7 N9 patients has been linked to a poor prognosis and death;however,the underlying mechanism that triggers the cytokine storm is ***,we found that efficient replication of the H7 N9 virus in mouse lungs activates gasdermin E(GSDME)-mediated pyroptosis in alveolar epithelial cells,and that the released cytosolic contents then trigger a cytokine *** of Gsdme switched the manner of death of A549 and human primary alveolar epithelial cells from pyroptosis to apoptosis upon H7 N9 virus infection,and Gsdme knockout mice survived H7 N9 virus lethal *** findings reveal that GSDME activation is a key and unique mechanism for the pulmonary cytokine storm and lethal outcome of H7 N9 virus infection and thus opens a new door for the development of antivirals against the H7 N9 virus.

关键词： H7N9 virus cytokine storm gasdermin E pyroptosis