Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing
Identifieur interne : 004153 ( Main/Curation ); précédent : 004152; suivant : 004154Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing
Auteurs : Hélène Raux [France] ; Patrice Coulon [France] ; Florence Lafay [France] ; Anne Flamand [France]Source :
- Virology [ 0042-6822 ] ; 1995.
Abstract
Abstract: Around 15% of our anti-glycoprotein monoclonal antibodies (MAbs) failed to neutralize the infectivity of the rabies virus during a 1-hr incubation at room temperature. In previous studies, we have demonstrated that it is possible to induce a massive conformational change of the glycoprotein population by incubating the virus at acidic pH. The conformational change is reversible and consequently viral infectivity is not affected by transient exposure at acidic pH. The proportion of glycoproteins in acidic or neutral configuration depends on the pH which means that even at neutral pH some glycoproteins transiently adopt the acidic configuration and vice versa. Here we report that some of our nonneutralizing MAbs recognize the acidic form of the glycoprotein at the virion surface. After incubation of the virus at pH 64, most glycoproteins are in the acidic configuration. Further 1-hr incubation with these MAbs at the same pH resulted in more immunoglobulins being attached to the virus and consequently neutralization was induced. It was also possible to induce neutralization with the same MAbs by incubation at neutral pH for a longer period or at a higher temperature. Mutants resistant to neutralization by these MAbs could be selected. Mutations confering resistance to neutralization were not localized in previously described antigenic sites and did not modify these sites at distance. They had no effect on the pathogenic power of the virus. Either they are situated in the epitope or they modify the epitope, so that it is no longer recognized by the antibody on the acidic configuration of the protein. Alternatively, these mutations may stabilize the protein in its neutral configuration. In addition, these experiments confirm our previous finding that neutralization requires the fixation of a large number of immunoglobulins on the virus, irrespective of the region of the protein recognized by the antibody.
Url:
DOI: 10.1006/viro.1995.1356
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001792
- to stream Istex, to step Curation: Pour aller vers cette notice dans l'étape Curation :001792
- to stream Istex, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :001844
- to stream Main, to step Merge: Pour aller vers cette notice dans l'étape Curation :004214
Links to Exploration step
ISTEX:B8E0F9FD5E5E04E5EFA7DF362D356C4962A91153Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing</title>
<author><name sortKey="Raux, Helene" sort="Raux, Helene" uniqKey="Raux H" first="Hélène" last="Raux">Hélène Raux</name>
</author>
<author><name sortKey="Coulon, Patrice" sort="Coulon, Patrice" uniqKey="Coulon P" first="Patrice" last="Coulon">Patrice Coulon</name>
</author>
<author><name sortKey="Lafay, Florence" sort="Lafay, Florence" uniqKey="Lafay F" first="Florence" last="Lafay">Florence Lafay</name>
</author>
<author><name sortKey="Flamand, Anne" sort="Flamand, Anne" uniqKey="Flamand A" first="Anne" last="Flamand">Anne Flamand</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:B8E0F9FD5E5E04E5EFA7DF362D356C4962A91153</idno>
<date when="1995" year="1995">1995</date>
<idno type="doi">10.1006/viro.1995.1356</idno>
<idno type="url">https://api.istex.fr/ark:/67375/6H6-M79CK2LN-Q/fulltext.pdf</idno>
<idno type="wicri:Area/Istex/Corpus">001792</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001792</idno>
<idno type="wicri:Area/Istex/Curation">001792</idno>
<idno type="wicri:Area/Istex/Checkpoint">001844</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001844</idno>
<idno type="wicri:doubleKey">0042-6822:1995:Raux H:monoclonal:antibodies:which</idno>
<idno type="wicri:Area/Main/Merge">004214</idno>
<idno type="wicri:Area/Main/Curation">004153</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing</title>
<author><name sortKey="Raux, Helene" sort="Raux, Helene" uniqKey="Raux H" first="Hélène" last="Raux">Hélène Raux</name>
<affiliation wicri:level="3"><country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Génétique des Virus, CNRS, 91198 GIF Cedex</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">GIF</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Coulon, Patrice" sort="Coulon, Patrice" uniqKey="Coulon P" first="Patrice" last="Coulon">Patrice Coulon</name>
<affiliation wicri:level="3"><country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Génétique des Virus, CNRS, 91198 GIF Cedex</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">GIF</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lafay, Florence" sort="Lafay, Florence" uniqKey="Lafay F" first="Florence" last="Lafay">Florence Lafay</name>
<affiliation wicri:level="3"><country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Génétique des Virus, CNRS, 91198 GIF Cedex</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">GIF</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Flamand, Anne" sort="Flamand, Anne" uniqKey="Flamand A" first="Anne" last="Flamand">Anne Flamand</name>
<affiliation wicri:level="3"><country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Génétique des Virus, CNRS, 91198 GIF Cedex</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">GIF</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Virology</title>
<title level="j" type="abbrev">YVIRO</title>
<idno type="ISSN">0042-6822</idno>
<imprint><publisher>ELSEVIER</publisher>
<date type="published" when="1995">1995</date>
<biblScope unit="volume">210</biblScope>
<biblScope unit="issue">2</biblScope>
<biblScope unit="page" from="400">400</biblScope>
<biblScope unit="page" to="408">408</biblScope>
</imprint>
<idno type="ISSN">0042-6822</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0042-6822</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass></textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Abstract: Around 15% of our anti-glycoprotein monoclonal antibodies (MAbs) failed to neutralize the infectivity of the rabies virus during a 1-hr incubation at room temperature. In previous studies, we have demonstrated that it is possible to induce a massive conformational change of the glycoprotein population by incubating the virus at acidic pH. The conformational change is reversible and consequently viral infectivity is not affected by transient exposure at acidic pH. The proportion of glycoproteins in acidic or neutral configuration depends on the pH which means that even at neutral pH some glycoproteins transiently adopt the acidic configuration and vice versa. Here we report that some of our nonneutralizing MAbs recognize the acidic form of the glycoprotein at the virion surface. After incubation of the virus at pH 64, most glycoproteins are in the acidic configuration. Further 1-hr incubation with these MAbs at the same pH resulted in more immunoglobulins being attached to the virus and consequently neutralization was induced. It was also possible to induce neutralization with the same MAbs by incubation at neutral pH for a longer period or at a higher temperature. Mutants resistant to neutralization by these MAbs could be selected. Mutations confering resistance to neutralization were not localized in previously described antigenic sites and did not modify these sites at distance. They had no effect on the pathogenic power of the virus. Either they are situated in the epitope or they modify the epitope, so that it is no longer recognized by the antibody on the acidic configuration of the protein. Alternatively, these mutations may stabilize the protein in its neutral configuration. In addition, these experiments confirm our previous finding that neutralization requires the fixation of a large number of immunoglobulins on the virus, irrespective of the region of the protein recognized by the antibody.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 004153 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Curation/biblio.hfd -nk 004153 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= Main |étape= Curation |type= RBID |clé= ISTEX:B8E0F9FD5E5E04E5EFA7DF362D356C4962A91153 |texte= Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing }}
This area was generated with Dilib version V0.6.33. |