Use of single-gene reassortant viruses to study the role of avian influenza A virus genes in attenuation of wild-type human influenza A virus for squirrel monkeys and adult human volunteers.
Identifieur interne : 001F25 ( Main/Exploration ); précédent : 001F24; suivant : 001F26Use of single-gene reassortant viruses to study the role of avian influenza A virus genes in attenuation of wild-type human influenza A virus for squirrel monkeys and adult human volunteers.
Auteurs : M L Clements [États-Unis] ; E K Subbarao ; L F Fries ; R A Karron ; W T London ; B R MurphySource :
- Journal of clinical microbiology [ 0095-1137 ] ; 1992.
Descripteurs français
- KwdFr :
- ARN viral (génétique), Adulte, Animaux, Données de séquences moléculaires, Gènes viraux, Humains, Réplication virale (génétique), Saimiri, Séquence nucléotidique, Transfection, Vaccins antigrippaux (isolement et purification), Vaccins atténués (isolement et purification), Virulence (génétique), Virus de la grippe A (génétique), Virus de la grippe A (pathogénicité), Virus de la grippe A (physiologie).
- MESH :
- génétique : ARN viral, Réplication virale, Virulence, Virus de la grippe A.
- isolement et purification : Vaccins antigrippaux, Vaccins atténués.
- pathogénicité : Virus de la grippe A.
- physiologie : Virus de la grippe A.
- Adulte, Animaux, Données de séquences moléculaires, Gènes viraux, Humains, Saimiri, Séquence nucléotidique, Transfection.
English descriptors
- KwdEn :
- Adult, Animals, Base Sequence, Genes, Viral, Humans, Influenza A virus (genetics), Influenza A virus (pathogenicity), Influenza A virus (physiology), Influenza Vaccines (isolation & purification), Molecular Sequence Data, RNA, Viral (genetics), Saimiri, Transfection, Vaccines, Attenuated (isolation & purification), Virulence (genetics), Virus Replication (genetics).
- MESH :
- chemical , genetics : RNA, Viral.
- chemical , isolation & purification : Influenza Vaccines, Vaccines, Attenuated.
- genetics : Influenza A virus, Virulence, Virus Replication.
- pathogenicity : Influenza A virus.
- physiology : Influenza A virus.
- Adult, Animals, Base Sequence, Genes, Viral, Humans, Molecular Sequence Data, Saimiri, Transfection.
Abstract
The transfer of six internal RNA segments from the avian influenza A/Mallard/New York/6750/78 (H2N2) virus reproducibly attenuates human influenza A viruses for squirrel monkeys and adult humans. To identify the avian influenza A virus genes that specify the attenuation and host range restriction of avian-human (ah) influenza A reassortant viruses (referred to as ah reassortants), we isolated six single-gene reassortant viruses (SGRs), each having a single internal RNA segment of the influenza A/Mallard/New York/6750/78 virus and seven RNA segments from the human influenza A/Los Angeles/2/87 (H3N2) wild-type virus. To assess the level of attenuation, we compared each SGR with the A/Los Angeles/2/87 wild-type virus and a 6-2 gene ah reassortant (having six internal RNA segments from the avian influenza A virus parent and two genes encoding the hemagglutinin and neuraminidase glycoproteins from the wild-type human influenza A virus) for the ability to replicate in seronegative squirrel monkeys and adult human volunteers. In monkeys and humans, replication of the 6-2 gene ah reassortant was highly restricted. In humans, the NS, M, PB2, and PB1 SGRs each replicated significantly less efficiently (P less than 0.05) than the wild-type human influenza A virus parent, suggesting that each of these genes contributes to the attenuation phenotype. In monkeys, only the NP, PB2, and possibly the M genes contributed to the attenuation phenotype. These discordant observations, particularly with regard to the NP SGR, indicate that not all genetic determinants of attenuation of influenza A viruses for humans can be identified during studies of SGRs conducted with monkeys. The PB2 and M SGRs that were attenuated in humans each exhibited a new phenotype that was not observed for either parental virus. Thus, it was not possible to determine whether avian influenza virus PB2 or M gene itself or a specific constellation of avian and human influenza A virus specified restriction of virus replication in humans.
PubMed: 1551982
Affiliations:
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Le document en format XML
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sortKey="Fries, L F" sort="Fries, L F" uniqKey="Fries L" first="L F" last="Fries">L F Fries</name></author><author><name sortKey="Karron, R A" sort="Karron, R A" uniqKey="Karron R" first="R A" last="Karron">R A Karron</name></author><author><name sortKey="London, W T" sort="London, W T" uniqKey="London W" first="W T" last="London">W T London</name></author><author><name sortKey="Murphy, B R" sort="Murphy, B R" uniqKey="Murphy B" first="B R" last="Murphy">B R Murphy</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1992">1992</date><idno type="RBID">pubmed:1551982</idno><idno type="pmid">1551982</idno><idno type="wicri:Area/PubMed/Corpus">000435</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000435</idno><idno type="wicri:Area/PubMed/Curation">000435</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000435</idno><idno 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Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Subbarao, E K" sort="Subbarao, E K" uniqKey="Subbarao E" first="E K" last="Subbarao">E K Subbarao</name></author><author><name sortKey="Fries, L F" sort="Fries, L F" uniqKey="Fries L" first="L F" last="Fries">L F Fries</name></author><author><name sortKey="Karron, R A" sort="Karron, R A" uniqKey="Karron R" first="R A" last="Karron">R A Karron</name></author><author><name sortKey="London, W T" sort="London, W T" uniqKey="London W" first="W T" last="London">W T London</name></author><author><name sortKey="Murphy, B R" sort="Murphy, B R" uniqKey="Murphy B" first="B R" last="Murphy">B R Murphy</name></author></analytic><series><title level="j">Journal of clinical microbiology</title><idno type="ISSN">0095-1137</idno><imprint><date when="1992" type="published">1992</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Animals</term><term>Base Sequence</term><term>Genes, Viral</term><term>Humans</term><term>Influenza A virus (genetics)</term><term>Influenza A virus (pathogenicity)</term><term>Influenza A virus (physiology)</term><term>Influenza Vaccines (isolation & purification)</term><term>Molecular Sequence Data</term><term>RNA, Viral (genetics)</term><term>Saimiri</term><term>Transfection</term><term>Vaccines, Attenuated (isolation & purification)</term><term>Virulence (genetics)</term><term>Virus Replication (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (génétique)</term><term>Adulte</term><term>Animaux</term><term>Données de séquences 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xml:lang="fr"><term>Adulte</term><term>Animaux</term><term>Données de séquences moléculaires</term><term>Gènes viraux</term><term>Humains</term><term>Saimiri</term><term>Séquence nucléotidique</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The transfer of six internal RNA segments from the avian influenza A/Mallard/New York/6750/78 (H2N2) virus reproducibly attenuates human influenza A viruses for squirrel monkeys and adult humans. To identify the avian influenza A virus genes that specify the attenuation and host range restriction of avian-human (ah) influenza A reassortant viruses (referred to as ah reassortants), we isolated six single-gene reassortant viruses (SGRs), each having a single internal RNA segment of the influenza A/Mallard/New York/6750/78 virus and seven RNA segments from the human influenza A/Los Angeles/2/87 (H3N2) wild-type virus. To assess the level of attenuation, we compared each SGR with the A/Los Angeles/2/87 wild-type virus and a 6-2 gene ah reassortant (having six internal RNA segments from the avian influenza A virus parent and two genes encoding the hemagglutinin and neuraminidase glycoproteins from the wild-type human influenza A virus) for the ability to replicate in seronegative squirrel monkeys and adult human volunteers. In monkeys and humans, replication of the 6-2 gene ah reassortant was highly restricted. In humans, the NS, M, PB2, and PB1 SGRs each replicated significantly less efficiently (P less than 0.05) than the wild-type human influenza A virus parent, suggesting that each of these genes contributes to the attenuation phenotype. In monkeys, only the NP, PB2, and possibly the M genes contributed to the attenuation phenotype. These discordant observations, particularly with regard to the NP SGR, indicate that not all genetic determinants of attenuation of influenza A viruses for humans can be identified during studies of SGRs conducted with monkeys. The PB2 and M SGRs that were attenuated in humans each exhibited a new phenotype that was not observed for either parental virus. Thus, it was not possible to determine whether avian influenza virus PB2 or M gene itself or a specific constellation of avian and human influenza A virus specified restriction of virus replication in humans.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="Fries, L F" sort="Fries, L F" uniqKey="Fries L" first="L F" last="Fries">L F Fries</name><name sortKey="Karron, R A" sort="Karron, R A" uniqKey="Karron R" first="R A" last="Karron">R A Karron</name><name sortKey="London, W T" sort="London, W T" uniqKey="London W" first="W T" last="London">W T London</name><name sortKey="Murphy, B R" sort="Murphy, B R" uniqKey="Murphy B" first="B R" last="Murphy">B R Murphy</name><name sortKey="Subbarao, E K" sort="Subbarao, E K" uniqKey="Subbarao E" first="E K" last="Subbarao">E K Subbarao</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Clements, M L" sort="Clements, M L" uniqKey="Clements M" first="M L" last="Clements">M L Clements</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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