An influenza A live attenuated reassortant virus possessing three temperature-sensitive mutations in the PB2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters.
Identifieur interne : 000390 ( PubMed/Corpus ); précédent : 000389; suivant : 000391An influenza A live attenuated reassortant virus possessing three temperature-sensitive mutations in the PB2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters.
Auteurs : B R Murphy ; E J Park ; P. Gottlieb ; K. SubbaraoSource :
- Vaccine [ 0264-410X ]
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Viral Proteins.
- chemical , immunology : Influenza Vaccines, Vaccines, Attenuated.
- immunology : Influenza A virus.
- Animals, Chickens, Chlorocebus aethiops, Cricetinae, Female, Mesocricetus, Mutation, RNA Replicase, Temperature, Transfection, Virus Replication.
Abstract
The purpose of the present study was to produce an influenza A H2N2 donor virus from which an attenuating PB2 gene bearing three discrete temperature sensitive (ts) mutations could be readily transferred to currently epidemic influenza A H1N1 and H3N2 viruses via genetic reassortment. An influenza A transfectant virus was first produced that contained site-directed ts mutations at amino acids 112, 265, and 556 in the PB2 gene of influenza A/AA/60 virus origin in a background of the other seven RNA segments from the influenza A/LA/87 (H3N2) virus. The A/LA/87 PB2 ts transfectant virus (clone 22B1) was mated with the A/AA/60 (H2N2) wild type virus, and six H2N2 ts reassortants were obtained. One reassortant virus, clone 25A1, possessed the triple ts PB2 gene in the context of all seven other genes of homologous A/AA/60 origin. Isolation of this reassortant permitted an examination of the contribution of the ts mutations present in a triple ts PB2 transfectant virus to its attenuation and phenotypic stability independent from an effect of the A/AA/60-A/LA/87 gene constellation on attenuation. It was found that the A/AA/60 triple ts reassortant virus was less ts, less attenuated, and less phenotypically stable than the A/LA/87 triple ts transfectant virus from which it was derived. The A/AA/60 reassortant possessing the PB2 gene containing three introduced ts mutations underwent rapid and significant loss of its temperature sensitivity following replication in the lungs of immunocompetent hamsters. This indicated that the A/AA/60-A/LA/87 gene constellation contributed significantly to the overall level of temperature-sensitivity, attenuation, and stability of the A/LA/87 triple ts transfectant virus. It is likely that the instability of the ts phenotype exhibited by the A/AA/60 triple ts reassortant virus would not be acceptable for a vaccine to be used in humans. The implications of these findings for the usefulness of ts mutations as the sole attenuating mutation in influenza virus vaccines is discussed.
DOI: 10.1016/s0264-410x(97)00031-5
PubMed: 9302747
Links to Exploration step
pubmed:9302747Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">An influenza A live attenuated reassortant virus possessing three temperature-sensitive mutations in the PB2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters.</title><author><name sortKey="Murphy, B R" sort="Murphy, B R" uniqKey="Murphy B" first="B R" last="Murphy">B R Murphy</name><affiliation><nlm:affiliation>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-0720, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Park, E J" sort="Park, E J" uniqKey="Park E" first="E J" last="Park">E J Park</name></author><author><name sortKey="Gottlieb, P" sort="Gottlieb, P" uniqKey="Gottlieb P" first="P" last="Gottlieb">P. Gottlieb</name></author><author><name sortKey="Subbarao, K" sort="Subbarao, K" uniqKey="Subbarao K" first="K" last="Subbarao">K. Subbarao</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="????"><PubDate><MedlineDate>1997 Aug-Sep</MedlineDate></PubDate></date><idno type="RBID">pubmed:9302747</idno><idno type="pmid">9302747</idno><idno type="doi">10.1016/s0264-410x(97)00031-5</idno><idno type="wicri:Area/PubMed/Corpus">000390</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000390</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">An influenza A live attenuated reassortant virus possessing three temperature-sensitive mutations in the PB2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters.</title><author><name sortKey="Murphy, B R" sort="Murphy, B R" uniqKey="Murphy B" first="B R" last="Murphy">B R Murphy</name><affiliation><nlm:affiliation>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-0720, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Park, E J" sort="Park, E J" uniqKey="Park E" first="E J" last="Park">E J Park</name></author><author><name sortKey="Gottlieb, P" sort="Gottlieb, P" uniqKey="Gottlieb P" first="P" last="Gottlieb">P. Gottlieb</name></author><author><name sortKey="Subbarao, K" sort="Subbarao, K" uniqKey="Subbarao K" first="K" last="Subbarao">K. Subbarao</name></author></analytic><series><title level="j">Vaccine</title><idno type="ISSN">0264-410X</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Chickens</term><term>Chlorocebus aethiops</term><term>Cricetinae</term><term>Female</term><term>Influenza A virus (immunology)</term><term>Influenza Vaccines (immunology)</term><term>Mesocricetus</term><term>Mutation</term><term>RNA Replicase</term><term>Temperature</term><term>Transfection</term><term>Vaccines, Attenuated (immunology)</term><term>Viral Proteins (genetics)</term><term>Virus Replication</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Influenza Vaccines</term><term>Vaccines, Attenuated</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chickens</term><term>Chlorocebus aethiops</term><term>Cricetinae</term><term>Female</term><term>Mesocricetus</term><term>Mutation</term><term>RNA Replicase</term><term>Temperature</term><term>Transfection</term><term>Virus Replication</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The purpose of the present study was to produce an influenza A H2N2 donor virus from which an attenuating PB2 gene bearing three discrete temperature sensitive (ts) mutations could be readily transferred to currently epidemic influenza A H1N1 and H3N2 viruses via genetic reassortment. An influenza A transfectant virus was first produced that contained site-directed ts mutations at amino acids 112, 265, and 556 in the PB2 gene of influenza A/AA/60 virus origin in a background of the other seven RNA segments from the influenza A/LA/87 (H3N2) virus. The A/LA/87 PB2 ts transfectant virus (clone 22B1) was mated with the A/AA/60 (H2N2) wild type virus, and six H2N2 ts reassortants were obtained. One reassortant virus, clone 25A1, possessed the triple ts PB2 gene in the context of all seven other genes of homologous A/AA/60 origin. Isolation of this reassortant permitted an examination of the contribution of the ts mutations present in a triple ts PB2 transfectant virus to its attenuation and phenotypic stability independent from an effect of the A/AA/60-A/LA/87 gene constellation on attenuation. It was found that the A/AA/60 triple ts reassortant virus was less ts, less attenuated, and less phenotypically stable than the A/LA/87 triple ts transfectant virus from which it was derived. The A/AA/60 reassortant possessing the PB2 gene containing three introduced ts mutations underwent rapid and significant loss of its temperature sensitivity following replication in the lungs of immunocompetent hamsters. This indicated that the A/AA/60-A/LA/87 gene constellation contributed significantly to the overall level of temperature-sensitivity, attenuation, and stability of the A/LA/87 triple ts transfectant virus. It is likely that the instability of the ts phenotype exhibited by the A/AA/60 triple ts reassortant virus would not be acceptable for a vaccine to be used in humans. The implications of these findings for the usefulness of ts mutations as the sole attenuating mutation in influenza virus vaccines is discussed.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">9302747</PMID><DateCompleted><Year>1997</Year><Month>10</Month><Day>23</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0264-410X</ISSN><JournalIssue CitedMedium="Print"><Volume>15</Volume><Issue>12-13</Issue><PubDate><MedlineDate>1997 Aug-Sep</MedlineDate></PubDate></JournalIssue><Title>Vaccine</Title><ISOAbbreviation>Vaccine</ISOAbbreviation></Journal><ArticleTitle>An influenza A live attenuated reassortant virus possessing three temperature-sensitive mutations in the PB2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters.</ArticleTitle><Pagination><MedlinePgn>1372-8</MedlinePgn></Pagination><Abstract><AbstractText>The purpose of the present study was to produce an influenza A H2N2 donor virus from which an attenuating PB2 gene bearing three discrete temperature sensitive (ts) mutations could be readily transferred to currently epidemic influenza A H1N1 and H3N2 viruses via genetic reassortment. An influenza A transfectant virus was first produced that contained site-directed ts mutations at amino acids 112, 265, and 556 in the PB2 gene of influenza A/AA/60 virus origin in a background of the other seven RNA segments from the influenza A/LA/87 (H3N2) virus. The A/LA/87 PB2 ts transfectant virus (clone 22B1) was mated with the A/AA/60 (H2N2) wild type virus, and six H2N2 ts reassortants were obtained. One reassortant virus, clone 25A1, possessed the triple ts PB2 gene in the context of all seven other genes of homologous A/AA/60 origin. Isolation of this reassortant permitted an examination of the contribution of the ts mutations present in a triple ts PB2 transfectant virus to its attenuation and phenotypic stability independent from an effect of the A/AA/60-A/LA/87 gene constellation on attenuation. It was found that the A/AA/60 triple ts reassortant virus was less ts, less attenuated, and less phenotypically stable than the A/LA/87 triple ts transfectant virus from which it was derived. The A/AA/60 reassortant possessing the PB2 gene containing three introduced ts mutations underwent rapid and significant loss of its temperature sensitivity following replication in the lungs of immunocompetent hamsters. This indicated that the A/AA/60-A/LA/87 gene constellation contributed significantly to the overall level of temperature-sensitivity, attenuation, and stability of the A/LA/87 triple ts transfectant virus. It is likely that the instability of the ts phenotype exhibited by the A/AA/60 triple ts reassortant virus would not be acceptable for a vaccine to be used in humans. The implications of these findings for the usefulness of ts mutations as the sole attenuating mutation in influenza virus vaccines is discussed.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Murphy</LastName><ForeName>B R</ForeName><Initials>BR</Initials><AffiliationInfo><Affiliation>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-0720, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>E J</ForeName><Initials>EJ</Initials></Author><Author ValidYN="Y"><LastName>Gottlieb</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Subbarao</LastName><ForeName>K</ForeName><Initials>K</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Vaccine</MedlineTA><NlmUniqueID>8406899</NlmUniqueID><ISSNLinking>0264-410X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007252">Influenza Vaccines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C057027">PB2 protein, Influenzavirus A</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014613">Vaccines, Attenuated</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.7.48</RegistryNumber><NameOfSubstance UI="D012324">RNA Replicase</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002645" MajorTopicYN="N">Chickens</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006224" MajorTopicYN="N">Cricetinae</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009980" MajorTopicYN="N">Influenza A virus</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007252" MajorTopicYN="N">Influenza Vaccines</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008647" MajorTopicYN="N">Mesocricetus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012324" MajorTopicYN="N">RNA Replicase</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013696" MajorTopicYN="N">Temperature</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014162" MajorTopicYN="N">Transfection</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014613" MajorTopicYN="N">Vaccines, Attenuated</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1997</Year><Month>8</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1997</Year><Month>9</Month><Day>26</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1997</Year><Month>8</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">9302747</ArticleId><ArticleId IdType="pii">S0264-410X(97)00031-5</ArticleId><ArticleId IdType="doi">10.1016/s0264-410x(97)00031-5</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000390 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 000390 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= PubMed
|étape= Corpus
|type= RBID
|clé= pubmed:9302747
|texte= An influenza A live attenuated reassortant virus possessing three temperature-sensitive mutations in the PB2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:9302747" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |