Molecular Signature of High Yield (Growth) Influenza A Virus Reassortants Prepared as Candidate Vaccine Seeds
Identifieur interne : 000865 ( Main/Exploration ); précédent : 000864; suivant : 000866Molecular Signature of High Yield (Growth) Influenza A Virus Reassortants Prepared as Candidate Vaccine Seeds
Auteurs : Manojkumar Ramanunninair [États-Unis] ; Jianhua Le [États-Unis] ; Shiroh Onodera [États-Unis] ; Andrew A. Fulvini [États-Unis] ; Barbara A. Pokorny [États-Unis] ; Jeanmarie Silverman [États-Unis] ; Rene Devis [États-Unis] ; Jennifer M. Arroyo [États-Unis] ; Yu He [États-Unis] ; Alex Boyne [États-Unis] ; Jayati Bera [États-Unis] ; Rebecca Halpin [États-Unis] ; Erin Hine [États-Unis] ; David J. Spiro [États-Unis] ; Doris Bucher [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Descripteurs français
- KwdFr :
- Génome viral (génétique), Humains, Hémagglutinines (génétique), Mutation, Sialidase (génétique), Sous-type H1N1 du virus de la grippe A (génétique), Sous-type H1N1 du virus de la grippe A (immunologie), Sous-type H3N2 du virus de la grippe A (génétique), Sous-type H3N2 du virus de la grippe A (immunologie), Sous-type H5N1 du virus de la grippe A (génétique), Sous-type H5N1 du virus de la grippe A (immunologie), Vaccins antigrippaux (génétique), Vaccins antigrippaux (immunologie), Virus de la grippe A (génétique), Virus de la grippe A (immunologie).
- MESH :
- génétique : Génome viral, Hémagglutinines, Sialidase, Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Sous-type H5N1 du virus de la grippe A, Vaccins antigrippaux, Virus de la grippe A.
- immunologie : Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Sous-type H5N1 du virus de la grippe A, Vaccins antigrippaux, Virus de la grippe A.
- Humains, Mutation.
English descriptors
- KwdEn :
- Genome, Viral (genetics), Hemagglutinins (genetics), Humans, Influenza A Virus, H1N1 Subtype (genetics), Influenza A Virus, H1N1 Subtype (immunology), Influenza A Virus, H3N2 Subtype (genetics), Influenza A Virus, H3N2 Subtype (immunology), Influenza A Virus, H5N1 Subtype (genetics), Influenza A Virus, H5N1 Subtype (immunology), Influenza A virus (genetics), Influenza A virus (immunology), Influenza Vaccines (genetics), Influenza Vaccines (immunology), Mutation, Neuraminidase (genetics).
- MESH :
- chemical , genetics : Hemagglutinins, Influenza Vaccines, Neuraminidase.
- genetics : Genome, Viral, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza A Virus, H5N1 Subtype, Influenza A virus.
- immunology : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza A Virus, H5N1 Subtype, Influenza A virus, Influenza Vaccines.
- Humans, Mutation.
Abstract
Human influenza virus isolates generally grow poorly in embryonated chicken eggs. Hence, gene reassortment of influenza A wild type (wt) viruses is performed with a highly egg adapted donor virus, A/Puerto Rico/8/1934 (PR8), to provide the high yield reassortant (HYR) viral ‘seeds’ for vaccine production. HYR must contain the hemagglutinin (HA) and neuraminidase (NA) genes of wt virus and one to six ‘internal’ genes from PR8. Most studies of influenza wt and HYRs have focused on the HA gene. The main objective of this study is the identification of the molecular signature in all eight gene segments of influenza A HYR candidate vaccine seeds associated with high growth
The genomes of 14 wt parental viruses, 23 HYRs (5 H1N1; 2, 1976 H1N1-SOIV; 2, 2009 H1N1pdm; 2 H2N2 and 12 H3N2) and PR8 were sequenced using the high-throughput sequencing pipeline with big dye terminator chemistry.
Silent and coding mutations were found in all internal genes derived from PR8 with the exception of the M gene. The M gene derived from PR8 was invariant in all 23 HYRs underlining the critical role of PR8 M in high yield phenotype. None of the wt virus derived internal genes had any silent change(s) except the PB1 gene in X-157. The highest number of recurrent silent and coding mutations was found in NS. With respect to the surface antigens, the majority of HYRs had coding mutations in HA; only 2 HYRs had coding mutations in NA.
In the era of application of reverse genetics to alter influenza A virus genomes, the mutations identified in the HYR gene segments associated with high growth
Url:
DOI: 10.1371/journal.pone.0065955
PubMed: 23776579
PubMed Central: 3679156
Affiliations:
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Fulvini</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Pokorny, Barbara A" sort="Pokorny, Barbara A" uniqKey="Pokorny B" first="Barbara A." last="Pokorny">Barbara A. Pokorny</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Silverman, Jeanmarie" sort="Silverman, Jeanmarie" uniqKey="Silverman J" first="Jeanmarie" last="Silverman">Jeanmarie Silverman</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Devis, Rene" sort="Devis, Rene" uniqKey="Devis R" first="Rene" last="Devis">Rene Devis</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Arroyo, Jennifer M" sort="Arroyo, Jennifer M" uniqKey="Arroyo J" first="Jennifer M." last="Arroyo">Jennifer M. Arroyo</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="He, Yu" sort="He, Yu" uniqKey="He Y" first="Yu" last="He">Yu He</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Boyne, Alex" sort="Boyne, Alex" uniqKey="Boyne A" first="Alex" last="Boyne">Alex Boyne</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Bera, Jayati" sort="Bera, Jayati" uniqKey="Bera J" first="Jayati" last="Bera">Jayati Bera</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Halpin, Rebecca" sort="Halpin, Rebecca" uniqKey="Halpin R" first="Rebecca" last="Halpin">Rebecca Halpin</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Hine, Erin" sort="Hine, Erin" uniqKey="Hine E" first="Erin" last="Hine">Erin Hine</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Spiro, David J" sort="Spiro, David J" uniqKey="Spiro D" first="David J." last="Spiro">David J. Spiro</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Influenza, SARS and Related Viral Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases, NIAID/NIH/DHHS, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Influenza, SARS and Related Viral Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases, NIAID/NIH/DHHS, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Bucher, Doris" sort="Bucher, Doris" uniqKey="Bucher D" first="Doris" last="Bucher">Doris Bucher</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, New York Medical College, Valhalla, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Genome, Viral (genetics)</term><term>Hemagglutinins (genetics)</term><term>Humans</term><term>Influenza A Virus, H1N1 Subtype (genetics)</term><term>Influenza A Virus, H1N1 Subtype (immunology)</term><term>Influenza A Virus, H3N2 Subtype (genetics)</term><term>Influenza A Virus, H3N2 Subtype (immunology)</term><term>Influenza A Virus, H5N1 Subtype (genetics)</term><term>Influenza A Virus, H5N1 Subtype (immunology)</term><term>Influenza A virus (genetics)</term><term>Influenza A virus (immunology)</term><term>Influenza Vaccines (genetics)</term><term>Influenza Vaccines (immunology)</term><term>Mutation</term><term>Neuraminidase (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Génome viral (génétique)</term><term>Humains</term><term>Hémagglutinines (génétique)</term><term>Mutation</term><term>Sialidase (génétique)</term><term>Sous-type H1N1 du virus de la grippe A (génétique)</term><term>Sous-type H1N1 du virus de la grippe A (immunologie)</term><term>Sous-type H3N2 du virus de la grippe A (génétique)</term><term>Sous-type H3N2 du virus de la grippe A (immunologie)</term><term>Sous-type H5N1 du virus de la grippe A (génétique)</term><term>Sous-type H5N1 du virus de la grippe A (immunologie)</term><term>Vaccins antigrippaux (génétique)</term><term>Vaccins antigrippaux (immunologie)</term><term>Virus de la grippe A (génétique)</term><term>Virus de la grippe A (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hemagglutinins</term><term>Influenza Vaccines</term><term>Neuraminidase</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genome, Viral</term><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term><term>Influenza A Virus, H5N1 Subtype</term><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Génome viral</term><term>Hémagglutinines</term><term>Sialidase</term><term>Sous-type H1N1 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Sous-type H5N1 du virus de la grippe A</term><term>Vaccins antigrippaux</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Sous-type H5N1 du virus de la grippe A</term><term>Vaccins antigrippaux</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term><term>Influenza A Virus, H5N1 Subtype</term><term>Influenza A virus</term><term>Influenza Vaccines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Mutation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Mutation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Human influenza virus isolates generally grow poorly in embryonated chicken eggs. Hence, gene reassortment of influenza A wild type (wt) viruses is performed with a highly egg adapted donor virus, A/Puerto Rico/8/1934 (PR8), to provide the high yield reassortant (HYR) viral ‘seeds’ for vaccine production. HYR must contain the hemagglutinin (HA) and neuraminidase (NA) genes of wt virus and one to six ‘internal’ genes from PR8. Most studies of influenza wt and HYRs have focused on the HA gene. The main objective of this study is the identification of the molecular signature in all eight gene segments of influenza A HYR candidate vaccine seeds associated with high growth <italic>in ovo.</italic></p></sec><sec><title>Methodology</title><p>The genomes of 14 wt parental viruses, 23 HYRs (5 H1N1; 2, 1976 H1N1-SOIV; 2, 2009 H1N1pdm; 2 H2N2 and 12 H3N2) and PR8 were sequenced using the high-throughput sequencing pipeline with big dye terminator chemistry.</p></sec><sec><title>Results</title><p>Silent and coding mutations were found in all internal genes derived from PR8 with the exception of the M gene. The M gene derived from PR8 was invariant in all 23 HYRs underlining the critical role of PR8 M in high yield phenotype. None of the wt virus derived internal genes had any silent change(s) except the PB1 gene in X-157. The highest number of recurrent silent and coding mutations was found in NS. With respect to the surface antigens, the majority of HYRs had coding mutations in HA; only 2 HYRs had coding mutations in NA.</p></sec><sec><title>Significance</title><p>In the era of application of reverse genetics to alter influenza A virus genomes, the mutations identified in the HYR gene segments associated with high growth <italic>in ovo</italic> may be of great practical benefit to modify PR8 and/or wt virus gene sequences for improved growth of vaccine ‘seed’ viruses.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lamb, Ra" uniqKey="Lamb R">RA Lamb</name></author><author><name sortKey="Choppin, Pw" uniqKey="Choppin P">PW Choppin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lazarowitz, Sg" uniqKey="Lazarowitz S">SG Lazarowitz</name></author><author><name sortKey="Compans, Rw" uniqKey="Compans R">RW Compans</name></author><author><name sortKey="Chopin, Pw" uniqKey="Chopin P">PW 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Arroyo</name><name sortKey="Bera, Jayati" sort="Bera, Jayati" uniqKey="Bera J" first="Jayati" last="Bera">Jayati Bera</name><name sortKey="Boyne, Alex" sort="Boyne, Alex" uniqKey="Boyne A" first="Alex" last="Boyne">Alex Boyne</name><name sortKey="Bucher, Doris" sort="Bucher, Doris" uniqKey="Bucher D" first="Doris" last="Bucher">Doris Bucher</name><name sortKey="Devis, Rene" sort="Devis, Rene" uniqKey="Devis R" first="Rene" last="Devis">Rene Devis</name><name sortKey="Fulvini, Andrew A" sort="Fulvini, Andrew A" uniqKey="Fulvini A" first="Andrew A." last="Fulvini">Andrew A. Fulvini</name><name sortKey="Halpin, Rebecca" sort="Halpin, Rebecca" uniqKey="Halpin R" first="Rebecca" last="Halpin">Rebecca Halpin</name><name sortKey="He, Yu" sort="He, Yu" uniqKey="He Y" first="Yu" last="He">Yu He</name><name sortKey="Hine, Erin" sort="Hine, Erin" uniqKey="Hine E" first="Erin" last="Hine">Erin Hine</name><name sortKey="Le, Jianhua" sort="Le, Jianhua" uniqKey="Le J" first="Jianhua" last="Le">Jianhua Le</name><name sortKey="Onodera, Shiroh" sort="Onodera, Shiroh" uniqKey="Onodera S" first="Shiroh" last="Onodera">Shiroh Onodera</name><name sortKey="Pokorny, Barbara A" sort="Pokorny, Barbara A" uniqKey="Pokorny B" first="Barbara A." last="Pokorny">Barbara A. Pokorny</name><name sortKey="Silverman, Jeanmarie" sort="Silverman, Jeanmarie" uniqKey="Silverman J" first="Jeanmarie" last="Silverman">Jeanmarie Silverman</name><name sortKey="Spiro, David J" sort="Spiro, David J" uniqKey="Spiro D" first="David J." last="Spiro">David J. 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