Antibody Epitopes on the Neuraminidase of a Recent H3N2 Influenza Virus (A/Memphis/31/98)
Identifieur interne : 001753 ( Main/Exploration ); précédent : 001752; suivant : 001754Antibody Epitopes on the Neuraminidase of a Recent H3N2 Influenza Virus (A/Memphis/31/98)
Auteurs : Upma Gulati [États-Unis] ; Chi-Ching Hwang [États-Unis] ; Lalitha Venkatramani [États-Unis] ; Shelly Gulati [États-Unis] ; Stephen J. Stray [États-Unis] ; Janis T. Lee [États-Unis] ; W. Graeme Laver [États-Unis] ; Alexey Bochkarev [États-Unis] ; Adam Zlotnick [États-Unis] ; Gillian M. Air [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2002.
Abstract
We have characterized monoclonal antibodies raised against the neuraminidase (NA) of a Sydney-like influenza virus (A/Memphis/31/98, H3N2) in a reassortant virus A/NWS/33HA-A/Mem/31/98NA (H1N2) and nine escape mutants selected by these monoclonal antibodies. Five of the antibodies use the same heavy chain VDJ genes and may not be independent. Another antibody, Mem5, uses the same VH and J genes with a different D gene and different isotype. Sequence changes in escape mutants selected by these antibodies occur in two loops of the NA, at amino acid 198, 199, 220, or 221. These amino acids are located on the opposite side of the NA monomer to the major epitopes found in N9 and early N2 NAs. Escape mutants with a change at 198 have reduced NA activity compared to the wild-type virus. Asp198 points toward the substrate binding pocket, and we had previously found that a site-directed mutation of this amino acid resulted in a loss of enzyme activity (M. R. Lentz, R. G. Webster, and G. M. Air, Biochemistry
Url:
DOI: 10.1128/JVI.76.23.12274-12280.2002
PubMed: 12414967
PubMed Central: 136895
Affiliations:
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Stray</name><affiliation wicri:level="2"><nlm:aff id="aff0">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oklahoma</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City</wicri:cityArea></affiliation></author><author><name sortKey="Lee, Janis T" sort="Lee, Janis T" uniqKey="Lee J" first="Janis T." last="Lee">Janis T. Lee</name><affiliation wicri:level="2"><nlm:aff id="aff0">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oklahoma</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City</wicri:cityArea></affiliation></author><author><name sortKey="Laver, W Graeme" sort="Laver, W Graeme" uniqKey="Laver W" first="W. Graeme" last="Laver">W. Graeme Laver</name><affiliation wicri:level="2"><nlm:aff id="aff0">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oklahoma</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City</wicri:cityArea></affiliation></author><author><name sortKey="Bochkarev, Alexey" sort="Bochkarev, Alexey" uniqKey="Bochkarev A" first="Alexey" last="Bochkarev">Alexey Bochkarev</name><affiliation wicri:level="2"><nlm:aff id="aff0">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oklahoma</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City</wicri:cityArea></affiliation></author><author><name sortKey="Zlotnick, Adam" sort="Zlotnick, Adam" uniqKey="Zlotnick A" first="Adam" last="Zlotnick">Adam Zlotnick</name><affiliation wicri:level="2"><nlm:aff id="aff0">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oklahoma</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City</wicri:cityArea></affiliation></author><author><name sortKey="Air, Gillian M" sort="Air, Gillian M" uniqKey="Air G" first="Gillian M." last="Air">Gillian M. Air</name><affiliation wicri:level="2"><nlm:aff id="aff0">Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oklahoma</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City</wicri:cityArea></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="2002">2002</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We have characterized monoclonal antibodies raised against the neuraminidase (NA) of a Sydney-like influenza virus (A/Memphis/31/98, H3N2) in a reassortant virus A/NWS/33<sub>HA</sub>-A/Mem/31/98<sub>NA</sub> (H1N2) and nine escape mutants selected by these monoclonal antibodies. Five of the antibodies use the same heavy chain VDJ genes and may not be independent. Another antibody, Mem5, uses the same V<sub>H</sub> and J genes with a different D gene and different isotype. Sequence changes in escape mutants selected by these antibodies occur in two loops of the NA, at amino acid 198, 199, 220, or 221. These amino acids are located on the opposite side of the NA monomer to the major epitopes found in N9 and early N2 NAs. Escape mutants with a change at 198 have reduced NA activity compared to the wild-type virus. Asp198 points toward the substrate binding pocket, and we had previously found that a site-directed mutation of this amino acid resulted in a loss of enzyme activity (M. R. Lentz, R. G. Webster, and G. M. Air, Biochemistry <bold>26:</bold>5351-5358, 1987). Mutations at residue 199, 220, or 221 did not alter the NA activity significantly compared to that of wild-type NA. A 3.5-Å structure of Mem5 Fab complexed with the Mem/98 NA shows that the Mem5 antibody binds at the sites of escape mutation selected by the other antibodies.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Oklahoma</li></region></list><tree><country name="États-Unis"><region name="Oklahoma"><name sortKey="Gulati, Upma" sort="Gulati, Upma" uniqKey="Gulati U" first="Upma" last="Gulati">Upma Gulati</name></region><name sortKey="Air, Gillian M" sort="Air, Gillian M" uniqKey="Air G" first="Gillian M." last="Air">Gillian M. Air</name><name sortKey="Bochkarev, Alexey" sort="Bochkarev, Alexey" uniqKey="Bochkarev A" first="Alexey" last="Bochkarev">Alexey Bochkarev</name><name sortKey="Gulati, Shelly" sort="Gulati, Shelly" uniqKey="Gulati S" first="Shelly" last="Gulati">Shelly Gulati</name><name sortKey="Hwang, Chi Ching" sort="Hwang, Chi Ching" uniqKey="Hwang C" first="Chi-Ching" last="Hwang">Chi-Ching Hwang</name><name sortKey="Laver, W Graeme" sort="Laver, W Graeme" uniqKey="Laver W" first="W. Graeme" last="Laver">W. Graeme Laver</name><name sortKey="Lee, Janis T" sort="Lee, Janis T" uniqKey="Lee J" first="Janis T." last="Lee">Janis T. Lee</name><name sortKey="Stray, Stephen J" sort="Stray, Stephen J" uniqKey="Stray S" first="Stephen J." last="Stray">Stephen J. Stray</name><name sortKey="Venkatramani, Lalitha" sort="Venkatramani, Lalitha" uniqKey="Venkatramani L" first="Lalitha" last="Venkatramani">Lalitha Venkatramani</name><name sortKey="Zlotnick, Adam" sort="Zlotnick, Adam" uniqKey="Zlotnick A" first="Adam" last="Zlotnick">Adam Zlotnick</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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