Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing
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 populati...
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Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 1995-07, Vol.210 (2), p.400-408 |
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description | 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. |
doi_str_mv | 10.1006/viro.1995.1356 |
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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.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1006/viro.1995.1356</identifier><identifier>PMID: 7542418</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Viral - immunology ; Antibody Specificity ; Antigens, Viral ; DNA Mutational Analysis ; Epitopes - chemistry ; Epitopes - immunology ; Female ; Glycoproteins - chemistry ; Glycoproteins - genetics ; Glycoproteins - immunology ; Hydrogen-Ion Concentration ; Mice ; Molecular Sequence Data ; Mutation - physiology ; Neutralization Tests ; Protein Conformation ; rabies virus ; Rabies virus - immunology ; Rabies virus - pathogenicity ; Viral Envelope Proteins - chemistry ; Viral Envelope Proteins - genetics ; Viral Envelope Proteins - immunology ; Virion - immunology</subject><ispartof>Virology (New York, N.Y.), 1995-07, Vol.210 (2), p.400-408</ispartof><rights>1995 Academic Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-1b3476dad1b45471142b33e4fb1e33e65b2c2461e3141484df745d3db9e6c4113</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0042682285713566$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7542418$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raux, Hélène</creatorcontrib><creatorcontrib>Coulon, Patrice</creatorcontrib><creatorcontrib>Lafay, Florence</creatorcontrib><creatorcontrib>Flamand, Anne</creatorcontrib><title>Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing</title><title>Virology (New York, N.Y.)</title><addtitle>Virology</addtitle><description>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.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>Antibody Specificity</subject><subject>Antigens, Viral</subject><subject>DNA Mutational Analysis</subject><subject>Epitopes - chemistry</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>Glycoproteins - chemistry</subject><subject>Glycoproteins - genetics</subject><subject>Glycoproteins - immunology</subject><subject>Hydrogen-Ion Concentration</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Mutation - physiology</subject><subject>Neutralization Tests</subject><subject>Protein Conformation</subject><subject>rabies virus</subject><subject>Rabies virus - immunology</subject><subject>Rabies virus - pathogenicity</subject><subject>Viral Envelope Proteins - chemistry</subject><subject>Viral Envelope Proteins - genetics</subject><subject>Viral Envelope Proteins - immunology</subject><subject>Virion - immunology</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EKkvhyg3JJ25ZPIkdJ8dlBQWpgFS-jpZjT3YHZe1iJ5Xan8CvJuku3BCn0ej90Ggexp6DWIMQ9asbSnENbavWUKn6AVuBaOtCVBIespUQsizqpiwfsyc5_xDzrrU4Y2dayVJCs2K_PsQQ3RCDHfgmjNRFT5j59z25Pb9CF3eB7pCPe-QbR54c38bQ025KdqQYeOzvtSvbLbGL4dbF6xRHpMDteC99nlJvHf5xfqO05LY28NfIP-I0JjvQHYXdU_aot0PGZ6d5zr6-ffNl-664_HTxfru5LJys2rGArpK69tZDJ5XUALLsqgpl3wHOs1Zd6UpZzwtIkI30vZbKV75rsXYSoDpnL4-986E_J8yjOVB2OAw2YJyy0VoKaIX-rxHqRipQajauj0aXYs4Je3Od6GDTrQFhFkpmoWQWSmahNAdenJqn7oD-r_2EZdabo47zH24Ik8mOMDj0lNCNxkf6V_VvCpOh7w</recordid><startdate>19950710</startdate><enddate>19950710</enddate><creator>Raux, Hélène</creator><creator>Coulon, Patrice</creator><creator>Lafay, Florence</creator><creator>Flamand, Anne</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19950710</creationdate><title>Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing</title><author>Raux, Hélène ; Coulon, Patrice ; Lafay, Florence ; Flamand, Anne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-1b3476dad1b45471142b33e4fb1e33e65b2c2461e3141484df745d3db9e6c4113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Viral - immunology</topic><topic>Antibody Specificity</topic><topic>Antigens, Viral</topic><topic>DNA Mutational Analysis</topic><topic>Epitopes - chemistry</topic><topic>Epitopes - immunology</topic><topic>Female</topic><topic>Glycoproteins - chemistry</topic><topic>Glycoproteins - genetics</topic><topic>Glycoproteins - immunology</topic><topic>Hydrogen-Ion Concentration</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Mutation - physiology</topic><topic>Neutralization Tests</topic><topic>Protein Conformation</topic><topic>rabies virus</topic><topic>Rabies virus - immunology</topic><topic>Rabies virus - pathogenicity</topic><topic>Viral Envelope Proteins - chemistry</topic><topic>Viral Envelope Proteins - genetics</topic><topic>Viral Envelope Proteins - immunology</topic><topic>Virion - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raux, Hélène</creatorcontrib><creatorcontrib>Coulon, Patrice</creatorcontrib><creatorcontrib>Lafay, Florence</creatorcontrib><creatorcontrib>Flamand, Anne</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Virology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raux, Hélène</au><au>Coulon, Patrice</au><au>Lafay, Florence</au><au>Flamand, Anne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing</atitle><jtitle>Virology (New York, N.Y.)</jtitle><addtitle>Virology</addtitle><date>1995-07-10</date><risdate>1995</risdate><volume>210</volume><issue>2</issue><spage>400</spage><epage>408</epage><pages>400-408</pages><issn>0042-6822</issn><eissn>1096-0341</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>7542418</pmid><doi>10.1006/viro.1995.1356</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Animals Antibodies, Monoclonal - immunology Antibodies, Viral - immunology Antibody Specificity Antigens, Viral DNA Mutational Analysis Epitopes - chemistry Epitopes - immunology Female Glycoproteins - chemistry Glycoproteins - genetics Glycoproteins - immunology Hydrogen-Ion Concentration Mice Molecular Sequence Data Mutation - physiology Neutralization Tests Protein Conformation rabies virus Rabies virus - immunology Rabies virus - pathogenicity Viral Envelope Proteins - chemistry Viral Envelope Proteins - genetics Viral Envelope Proteins - immunology Virion - immunology |
title | Monoclonal Antibodies Which Recognize the Acidic Configuration of the Rabies Glycoprotein at the Surface of the Virion Can Be Neutralizing |
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