A single M protein mutation affects the acid inactivation threshold and growth kinetics of a chimeric flavivirus
Abstract Numerous viruses of the Flaviviridae family, including dengue, yellow fever, Japanese encephalitis, and West Nile, cause significant disease in humans and animals. The structure and function of the molecular components of the flavivirus envelope are therefore of significant interest. To our...
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| Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2007-06, Vol.362 (2), p.468-474 |
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| creator | Maier, Caroline C Delagrave, Simon Zhang, Zhen-xi Brown, Nathan Monath, Thomas P Pugachev, Konstantin V Guirakhoo, Farshad |
| description | Abstract Numerous viruses of the Flaviviridae family, including dengue, yellow fever, Japanese encephalitis, and West Nile, cause significant disease in humans and animals. The structure and function of the molecular components of the flavivirus envelope are therefore of significant interest. To our knowledge, a membrane (M) protein mutation which affects the pH at which flavivirus particles are inactivated in vitro has never been reported. Here we show that substitution of proline for glutamine at residue M5 (MQ5P ) of a Japanese encephalitis–yellow fever chimera (ChimeriVax-JE) increases its acid sensitivity in vitro by 0.3 pH units (i.e., increases the pH at which virus titer is reduced by 50% from 6.08 to 6.38). In addition, growth kinetics of this mutant virus are accelerated in Vero cells, while neurovirulence and neuroinvasiveness measured in a mouse model are unaffected. A possible interpretation of these observations is that M can modulate the envelope (E) protein function during cell infection. |
| doi_str_mv | 10.1016/j.virol.2007.01.008 |
| format | Article |
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The structure and function of the molecular components of the flavivirus envelope are therefore of significant interest. To our knowledge, a membrane (M) protein mutation which affects the pH at which flavivirus particles are inactivated in vitro has never been reported. Here we show that substitution of proline for glutamine at residue M5 (MQ5P ) of a Japanese encephalitis–yellow fever chimera (ChimeriVax-JE) increases its acid sensitivity in vitro by 0.3 pH units (i.e., increases the pH at which virus titer is reduced by 50% from 6.08 to 6.38). In addition, growth kinetics of this mutant virus are accelerated in Vero cells, while neurovirulence and neuroinvasiveness measured in a mouse model are unaffected. A possible interpretation of these observations is that M can modulate the envelope (E) protein function during cell infection.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1016/j.virol.2007.01.008</identifier><identifier>PMID: 17303204</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acid inactivation ; Acids - pharmacology ; Amino Acid Substitution ; Animals ; Antiviral Agents - pharmacology ; Cercopithecus aethiops ; Chimera ; ChimeriVax ; Disease Models, Animal ; Encephalitis Virus, Japanese - drug effects ; Encephalitis Virus, Japanese - genetics ; Encephalitis Virus, Japanese - pathogenicity ; Envelope protein ; Flaviviridae ; Flavivirus ; Flavivirus Infections ; Infectious Disease ; Japanese encephalitis ; Japanese encephalitis virus ; Kinetics ; Membrane fusion ; Membrane protein ; Mice ; Microbial Viability ; Mutagenesis ; pathogenicity ; Premembrane protein ; Survival Analysis ; Vaccine ; Vero Cells ; viral envelope proteins ; Viral Matrix Proteins - genetics ; Viral Plaque Assay ; viral proteins ; Virulence ; Virus Inactivation ; Virus Replication ; West Nile Virus Vaccines ; Yellow fever ; Yellow fever virus ; Yellow fever virus - drug effects ; Yellow fever virus - genetics ; Yellow fever virus - pathogenicity</subject><ispartof>Virology (New York, N.Y.), 2007-06, Vol.362 (2), p.468-474</ispartof><rights>Elsevier Inc.</rights><rights>2007 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-d7bf34a53fc534bfaca3703dfc7a286cb26c876d974e62ce1c0af38e879e76e63</citedby><cites>FETCH-LOGICAL-c467t-d7bf34a53fc534bfaca3703dfc7a286cb26c876d974e62ce1c0af38e879e76e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.virol.2007.01.008$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17303204$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maier, Caroline C</creatorcontrib><creatorcontrib>Delagrave, Simon</creatorcontrib><creatorcontrib>Zhang, Zhen-xi</creatorcontrib><creatorcontrib>Brown, Nathan</creatorcontrib><creatorcontrib>Monath, Thomas P</creatorcontrib><creatorcontrib>Pugachev, Konstantin V</creatorcontrib><creatorcontrib>Guirakhoo, Farshad</creatorcontrib><title>A single M protein mutation affects the acid inactivation threshold and growth kinetics of a chimeric flavivirus</title><title>Virology (New York, N.Y.)</title><addtitle>Virology</addtitle><description>Abstract Numerous viruses of the Flaviviridae family, including dengue, yellow fever, Japanese encephalitis, and West Nile, cause significant disease in humans and animals. The structure and function of the molecular components of the flavivirus envelope are therefore of significant interest. To our knowledge, a membrane (M) protein mutation which affects the pH at which flavivirus particles are inactivated in vitro has never been reported. Here we show that substitution of proline for glutamine at residue M5 (MQ5P ) of a Japanese encephalitis–yellow fever chimera (ChimeriVax-JE) increases its acid sensitivity in vitro by 0.3 pH units (i.e., increases the pH at which virus titer is reduced by 50% from 6.08 to 6.38). In addition, growth kinetics of this mutant virus are accelerated in Vero cells, while neurovirulence and neuroinvasiveness measured in a mouse model are unaffected. A possible interpretation of these observations is that M can modulate the envelope (E) protein function during cell infection.</description><subject>Acid inactivation</subject><subject>Acids - pharmacology</subject><subject>Amino Acid Substitution</subject><subject>Animals</subject><subject>Antiviral Agents - pharmacology</subject><subject>Cercopithecus aethiops</subject><subject>Chimera</subject><subject>ChimeriVax</subject><subject>Disease Models, Animal</subject><subject>Encephalitis Virus, Japanese - drug effects</subject><subject>Encephalitis Virus, Japanese - genetics</subject><subject>Encephalitis Virus, Japanese - pathogenicity</subject><subject>Envelope protein</subject><subject>Flaviviridae</subject><subject>Flavivirus</subject><subject>Flavivirus Infections</subject><subject>Infectious Disease</subject><subject>Japanese encephalitis</subject><subject>Japanese encephalitis virus</subject><subject>Kinetics</subject><subject>Membrane fusion</subject><subject>Membrane protein</subject><subject>Mice</subject><subject>Microbial Viability</subject><subject>Mutagenesis</subject><subject>pathogenicity</subject><subject>Premembrane protein</subject><subject>Survival Analysis</subject><subject>Vaccine</subject><subject>Vero Cells</subject><subject>viral envelope proteins</subject><subject>Viral Matrix Proteins - genetics</subject><subject>Viral Plaque Assay</subject><subject>viral proteins</subject><subject>Virulence</subject><subject>Virus Inactivation</subject><subject>Virus Replication</subject><subject>West Nile Virus Vaccines</subject><subject>Yellow fever</subject><subject>Yellow fever virus</subject><subject>Yellow fever virus - drug effects</subject><subject>Yellow fever virus - genetics</subject><subject>Yellow fever virus - pathogenicity</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1vEzEQhlcIREPhFyCBT71lGdsbe3MAqar4koo4lJ4txzvOTrq7DrY3qP8eh0RC4sLJsvy8r8aPpqpec6g5cPVuVx8ohqEWALoGXgO0T6oFh7Vagmz402oB0IilaoW4qF6ktINy1xqeVxdcS5ACmkW1v2aJpu2A7Bvbx5CRJjbO2WYKE7Peo8uJ5R6ZddQxmqzLdDi95j5i6sPQMTt1bBvDr9yzB5owk0sseGaZ62nESI75wR6ojDunl9Uzb4eEr87nZXX_6eOPmy_L2--fv95c3y5do3RednrjZWNX0ruVbDbeOis1yM47bUWr3EYo12rVrXWDSjjkDqyXLbZ6jVqhkpfV1am3_OrnjCmbkZLDYbAThjkZvlZatSAKKE-giyGliN7sI402PhoO5ija7Mwf0eYo2gA3RXRJvTnXz5sRu7-Zs9kCvD0B3gZjt5GSub8TwGUpaYXkq0K8PxFYNBwIo0mOcHLYUSzaTRfoPyN8-CfvBprI2eEBHzHtwhynYthwk4QBc3fchuMygC6LIJpG_gaB5rA2</recordid><startdate>20070605</startdate><enddate>20070605</enddate><creator>Maier, Caroline C</creator><creator>Delagrave, Simon</creator><creator>Zhang, Zhen-xi</creator><creator>Brown, Nathan</creator><creator>Monath, Thomas P</creator><creator>Pugachev, Konstantin V</creator><creator>Guirakhoo, Farshad</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20070605</creationdate><title>A single M protein mutation affects the acid inactivation threshold and growth kinetics of a chimeric flavivirus</title><author>Maier, Caroline C ; Delagrave, Simon ; Zhang, Zhen-xi ; Brown, Nathan ; Monath, Thomas P ; Pugachev, Konstantin V ; Guirakhoo, Farshad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-d7bf34a53fc534bfaca3703dfc7a286cb26c876d974e62ce1c0af38e879e76e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acid inactivation</topic><topic>Acids - pharmacology</topic><topic>Amino Acid Substitution</topic><topic>Animals</topic><topic>Antiviral Agents - pharmacology</topic><topic>Cercopithecus aethiops</topic><topic>Chimera</topic><topic>ChimeriVax</topic><topic>Disease Models, Animal</topic><topic>Encephalitis Virus, Japanese - drug effects</topic><topic>Encephalitis Virus, Japanese - genetics</topic><topic>Encephalitis Virus, Japanese - pathogenicity</topic><topic>Envelope protein</topic><topic>Flaviviridae</topic><topic>Flavivirus</topic><topic>Flavivirus Infections</topic><topic>Infectious Disease</topic><topic>Japanese encephalitis</topic><topic>Japanese encephalitis virus</topic><topic>Kinetics</topic><topic>Membrane fusion</topic><topic>Membrane protein</topic><topic>Mice</topic><topic>Microbial Viability</topic><topic>Mutagenesis</topic><topic>pathogenicity</topic><topic>Premembrane protein</topic><topic>Survival Analysis</topic><topic>Vaccine</topic><topic>Vero Cells</topic><topic>viral envelope proteins</topic><topic>Viral Matrix Proteins - genetics</topic><topic>Viral Plaque Assay</topic><topic>viral proteins</topic><topic>Virulence</topic><topic>Virus Inactivation</topic><topic>Virus Replication</topic><topic>West Nile Virus Vaccines</topic><topic>Yellow fever</topic><topic>Yellow fever virus</topic><topic>Yellow fever virus - drug effects</topic><topic>Yellow fever virus - genetics</topic><topic>Yellow fever virus - pathogenicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maier, Caroline C</creatorcontrib><creatorcontrib>Delagrave, Simon</creatorcontrib><creatorcontrib>Zhang, Zhen-xi</creatorcontrib><creatorcontrib>Brown, Nathan</creatorcontrib><creatorcontrib>Monath, Thomas P</creatorcontrib><creatorcontrib>Pugachev, Konstantin V</creatorcontrib><creatorcontrib>Guirakhoo, Farshad</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences 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>Genetics Abstracts</collection><jtitle>Virology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maier, Caroline C</au><au>Delagrave, Simon</au><au>Zhang, Zhen-xi</au><au>Brown, Nathan</au><au>Monath, Thomas P</au><au>Pugachev, Konstantin V</au><au>Guirakhoo, Farshad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A single M protein mutation affects the acid inactivation threshold and growth kinetics of a chimeric flavivirus</atitle><jtitle>Virology (New York, N.Y.)</jtitle><addtitle>Virology</addtitle><date>2007-06-05</date><risdate>2007</risdate><volume>362</volume><issue>2</issue><spage>468</spage><epage>474</epage><pages>468-474</pages><issn>0042-6822</issn><eissn>1096-0341</eissn><abstract>Abstract Numerous viruses of the Flaviviridae family, including dengue, yellow fever, Japanese encephalitis, and West Nile, cause significant disease in humans and animals. The structure and function of the molecular components of the flavivirus envelope are therefore of significant interest. To our knowledge, a membrane (M) protein mutation which affects the pH at which flavivirus particles are inactivated in vitro has never been reported. Here we show that substitution of proline for glutamine at residue M5 (MQ5P ) of a Japanese encephalitis–yellow fever chimera (ChimeriVax-JE) increases its acid sensitivity in vitro by 0.3 pH units (i.e., increases the pH at which virus titer is reduced by 50% from 6.08 to 6.38). In addition, growth kinetics of this mutant virus are accelerated in Vero cells, while neurovirulence and neuroinvasiveness measured in a mouse model are unaffected. A possible interpretation of these observations is that M can modulate the envelope (E) protein function during cell infection.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17303204</pmid><doi>10.1016/j.virol.2007.01.008</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Virology (New York, N.Y.), 2007-06, Vol.362 (2), p.468-474 |
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| subjects | Acid inactivation Acids - pharmacology Amino Acid Substitution Animals Antiviral Agents - pharmacology Cercopithecus aethiops Chimera ChimeriVax Disease Models, Animal Encephalitis Virus, Japanese - drug effects Encephalitis Virus, Japanese - genetics Encephalitis Virus, Japanese - pathogenicity Envelope protein Flaviviridae Flavivirus Flavivirus Infections Infectious Disease Japanese encephalitis Japanese encephalitis virus Kinetics Membrane fusion Membrane protein Mice Microbial Viability Mutagenesis pathogenicity Premembrane protein Survival Analysis Vaccine Vero Cells viral envelope proteins Viral Matrix Proteins - genetics Viral Plaque Assay viral proteins Virulence Virus Inactivation Virus Replication West Nile Virus Vaccines Yellow fever Yellow fever virus Yellow fever virus - drug effects Yellow fever virus - genetics Yellow fever virus - pathogenicity |
| title | A single M protein mutation affects the acid inactivation threshold and growth kinetics of a chimeric flavivirus |
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