Attenuation of influenza A virus by insertion of a foreign epitope into the neuraminidase.
Identifieur interne : 001F30 ( Main/Exploration ); précédent : 001F29; suivant : 001F31Attenuation of influenza A virus by insertion of a foreign epitope into the neuraminidase.
Auteurs : M R Castrucci ; P. Bilsel ; Yoshihiro Kawaoka [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 1992.
Abstract
As the initial step in generating a live attenuated influenza A vaccine, we attempted to substitute an unrelated amino acid sequence (FLAG) for a portion of the neuraminidase (NA) molecule in influenza virus A/WSN/33 (H1N1), using a recently developed technique (reverse genetics [W. Luytjes, M. Krystal, M. Enami, J. D. Parvin, and P. Palese, Cell 59:1107-1113, 1989]). This technique allowed us to rescue the NA molecules containing the FLAG sequence (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys) at the bottom portion of the boxlike head of the molecule immediately above the stalk region (amino acid residues 63 to 70 [WSN NA numbering]). An anti-FLAG monoclonal antibody immunoprecipitated the NA molecules with the FLAG sequence, demonstrating that the foreign epitope was exposed on the virion surface. The dose of FLAG-containing transfectant virus required to kill 50% of mice was 100-fold higher than the required dose of parent virus. The FLAG sequence was stably maintained in the NA molecule during passage of the virus in tissue culture and in mice. These findings demonstrate that live influenza A vaccine strains with stable attenuating mutations in the coding region of the viral genes can be generated by reverse genetics.
Url:
PubMed: 1378505
PubMed Central: 241288
Affiliations:
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Bilsel</name></author><author><name sortKey="Kawaoka, Y" sort="Kawaoka, Y" uniqKey="Kawaoka Y" first="Y" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation><country>États-Unis</country><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">1378505</idno><idno type="pmc">241288</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC241288</idno><idno type="RBID">PMC:241288</idno><date when="1992">1992</date><idno type="wicri:Area/Pmc/Corpus">000389</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000389</idno><idno type="wicri:Area/Pmc/Curation">000389</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000389</idno><idno type="wicri:Area/Pmc/Checkpoint">000D13</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000D13</idno><idno type="wicri:Area/Ncbi/Merge">000082</idno><idno type="wicri:Area/Ncbi/Curation">000082</idno><idno type="wicri:Area/Ncbi/Checkpoint">000082</idno><idno type="wicri:doubleKey">0022-538X:1992:Castrucci M:attenuation:of:influenza</idno><idno type="wicri:Area/Main/Merge">002025</idno><idno type="wicri:Area/Main/Curation">001F30</idno><idno type="wicri:Area/Main/Exploration">001F30</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Attenuation of influenza A virus by insertion of a foreign epitope into the neuraminidase.</title><author><name sortKey="Castrucci, M R" sort="Castrucci, M R" uniqKey="Castrucci M" first="M R" last="Castrucci">M R Castrucci</name></author><author><name sortKey="Bilsel, P" sort="Bilsel, P" uniqKey="Bilsel P" first="P" last="Bilsel">P. Bilsel</name></author><author><name sortKey="Kawaoka, Y" sort="Kawaoka, Y" uniqKey="Kawaoka Y" first="Y" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation><country>États-Unis</country><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></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="1992">1992</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>As the initial step in generating a live attenuated influenza A vaccine, we attempted to substitute an unrelated amino acid sequence (FLAG) for a portion of the neuraminidase (NA) molecule in influenza virus A/WSN/33 (H1N1), using a recently developed technique (reverse genetics [W. Luytjes, M. Krystal, M. Enami, J. D. Parvin, and P. Palese, Cell 59:1107-1113, 1989]). This technique allowed us to rescue the NA molecules containing the FLAG sequence (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys) at the bottom portion of the boxlike head of the molecule immediately above the stalk region (amino acid residues 63 to 70 [WSN NA numbering]). An anti-FLAG monoclonal antibody immunoprecipitated the NA molecules with the FLAG sequence, demonstrating that the foreign epitope was exposed on the virion surface. The dose of FLAG-containing transfectant virus required to kill 50% of mice was 100-fold higher than the required dose of parent virus. The FLAG sequence was stably maintained in the NA molecule during passage of the virus in tissue culture and in mice. These findings demonstrate that live influenza A vaccine strains with stable attenuating mutations in the coding region of the viral genes can be generated by reverse genetics.</p><sec sec-type="scanned-figures"><title>Images</title><fig id="F1"><graphic xlink:href="jvirol00040-0034-a" xlink:role="4648"></graphic></fig><fig id="F2"><graphic xlink:href="jvirol00040-0036-a" xlink:role="4650"></graphic></fig><fig id="F3"><graphic xlink:href="jvirol00040-0037-a" xlink:role="4651"></graphic></fig></sec></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Wisconsin</li></region><settlement><li>Madison (Wisconsin)</li></settlement><orgName><li>Université du Wisconsin à Madison</li></orgName></list><tree><noCountry><name sortKey="Bilsel, P" sort="Bilsel, P" uniqKey="Bilsel P" first="P" last="Bilsel">P. Bilsel</name><name sortKey="Castrucci, M R" sort="Castrucci, M R" uniqKey="Castrucci M" first="M R" last="Castrucci">M R Castrucci</name></noCountry><country name="États-Unis"><region name="Wisconsin"><name sortKey="Kawaoka, Y" sort="Kawaoka, Y" uniqKey="Kawaoka Y" first="Y" last="Kawaoka">Yoshihiro Kawaoka</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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