A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs
Identifieur interne : 000351 ( Main/Exploration ); précédent : 000350; suivant : 000352A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs
Auteurs : Zeng Wang [République populaire de Chine] ; Huanliang Yang [République populaire de Chine] ; Yan Chen [République populaire de Chine] ; Shiyu Tao [République populaire de Chine] ; Liling Liu [République populaire de Chine] ; Huihui Kong [République populaire de Chine] ; Shujie Ma [République populaire de Chine] ; Fei Meng [République populaire de Chine] ; Yasuo Suzuki [Japon] ; Chuanling Qiao [République populaire de Chine] ; Hualan Chen [République populaire de Chine]Source :
- Journal of Virology [ 0022-538X ] ; 2017.
Abstract
Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains.
Url:
DOI: 10.1128/JVI.00800-17
PubMed: 28814518
PubMed Central: 5640871
Affiliations:
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Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Suzuki, Yasuo" sort="Suzuki, Yasuo" uniqKey="Suzuki Y" first="Yasuo" last="Suzuki">Yasuo Suzuki</name><affiliation wicri:level="1"><nlm:aff id="aff2">College of Life and Health Sciences, Chubu University, Aichi, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>College of Life and Health Sciences, Chubu University, Aichi</wicri:regionArea><wicri:noRegion>Aichi</wicri:noRegion></affiliation></author><author><name sortKey="Qiao, Chuanling" sort="Qiao, Chuanling" uniqKey="Qiao C" first="Chuanling" last="Qiao">Chuanling 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Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Huanliang" sort="Yang, Huanliang" uniqKey="Yang H" first="Huanliang" last="Yang">Huanliang Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yan" sort="Chen, Yan" uniqKey="Chen Y" first="Yan" last="Chen">Yan Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Tao, Shiyu" sort="Tao, Shiyu" uniqKey="Tao S" first="Shiyu" last="Tao">Shiyu Tao</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Liling" sort="Liu, Liling" uniqKey="Liu L" first="Liling" last="Liu">Liling Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Kong, Huihui" sort="Kong, Huihui" uniqKey="Kong H" first="Huihui" last="Kong">Huihui Kong</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Shujie" sort="Ma, Shujie" uniqKey="Ma S" first="Shujie" last="Ma">Shujie Ma</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Meng, Fei" sort="Meng, Fei" uniqKey="Meng F" first="Fei" last="Meng">Fei Meng</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Suzuki, Yasuo" sort="Suzuki, Yasuo" uniqKey="Suzuki Y" first="Yasuo" last="Suzuki">Yasuo Suzuki</name><affiliation wicri:level="1"><nlm:aff id="aff2">College of Life and Health Sciences, Chubu University, Aichi, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>College of Life and Health Sciences, Chubu University, Aichi</wicri:regionArea><wicri:noRegion>Aichi</wicri:noRegion></affiliation></author><author><name sortKey="Qiao, Chuanling" sort="Qiao, Chuanling" uniqKey="Qiao C" first="Chuanling" last="Qiao">Chuanling Qiao</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Hualan" sort="Chen, Hualan" uniqKey="Chen H" first="Hualan" last="Chen">Hualan Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin</wicri:regionArea><wicri:noRegion>Harbin</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains.</p><p><bold>IMPORTANCE</bold> Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus affinity for human-type receptors. In this study, we explored the genetic basis of the transmissibility difference between two Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses in guinea pigs and found that the amino acid glutamic acid at position 225 in the HA1 protein plays a critical role in the transmission of EAH1N1 virus by increasing the efficiency of viral assembly and budding.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author><author><name sortKey="Krauss, S" uniqKey="Krauss S">S Krauss</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garten, Rj" uniqKey="Garten R">RJ Garten</name></author><author><name sortKey="Davis, Ct" uniqKey="Davis C">CT Davis</name></author><author><name sortKey="Russell, Ca" uniqKey="Russell C">CA Russell</name></author><author><name sortKey="Shu, B" 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Yun</name></author><author><name sortKey="Cho, Wi" uniqKey="Cho W">WI Cho</name></author><author><name sortKey="Kim, Y S" uniqKey="Kim Y">Y-S Kim</name></author><author><name sortKey="Ko, Yy" uniqKey="Ko Y">YY Ko</name></author><author><name sortKey="Park, M S" uniqKey="Park M">M-S Park</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Japon</li><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Zeng" sort="Wang, Zeng" uniqKey="Wang Z" first="Zeng" last="Wang">Zeng Wang</name></noRegion><name sortKey="Chen, Hualan" sort="Chen, Hualan" uniqKey="Chen H" first="Hualan" last="Chen">Hualan Chen</name><name sortKey="Chen, Yan" sort="Chen, Yan" uniqKey="Chen Y" first="Yan" last="Chen">Yan Chen</name><name sortKey="Kong, Huihui" sort="Kong, Huihui" uniqKey="Kong H" first="Huihui" last="Kong">Huihui Kong</name><name sortKey="Liu, Liling" sort="Liu, Liling" uniqKey="Liu L" first="Liling" last="Liu">Liling Liu</name><name sortKey="Ma, Shujie" sort="Ma, Shujie" uniqKey="Ma S" first="Shujie" last="Ma">Shujie Ma</name><name sortKey="Meng, Fei" sort="Meng, Fei" uniqKey="Meng F" first="Fei" last="Meng">Fei Meng</name><name sortKey="Qiao, Chuanling" sort="Qiao, Chuanling" uniqKey="Qiao C" first="Chuanling" last="Qiao">Chuanling Qiao</name><name sortKey="Tao, Shiyu" sort="Tao, Shiyu" uniqKey="Tao S" first="Shiyu" last="Tao">Shiyu Tao</name><name sortKey="Yang, Huanliang" sort="Yang, Huanliang" uniqKey="Yang H" first="Huanliang" last="Yang">Huanliang Yang</name></country><country name="Japon"><noRegion><name sortKey="Suzuki, Yasuo" sort="Suzuki, Yasuo" uniqKey="Suzuki Y" first="Yasuo" last="Suzuki">Yasuo Suzuki</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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