A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis
Abstract An adaptive mutation (E249G) within West Nile virus (WNV) NS4B gene was consistently recovered from replicon RNAs in C3H/He mouse cells. The E249G is located at the C-terminal tail of NS4B predicted to be on the cytoplasmic side of the endoplasmic reticulum membrane. The E249G substitution...
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| Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2007-04, Vol.361 (1), p.229-241 |
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| creator | Puig-Basagoiti, Francesc Tilgner, Mark Bennett, Corey J Zhou, Yangsheng Muñoz-Jordán, Jorge L García-Sastre, Adolfo Bernard, Kristen A Shi, Pei-Yong |
| description | Abstract An adaptive mutation (E249G) within West Nile virus (WNV) NS4B gene was consistently recovered from replicon RNAs in C3H/He mouse cells. The E249G is located at the C-terminal tail of NS4B predicted to be on the cytoplasmic side of the endoplasmic reticulum membrane. The E249G substitution reduced replicon RNA synthesis. Compared with the wild-type NS4B, the E249G mutant protein exhibited a similar efficiency in evasion of interferon-β response. Recombinant E249G virus exhibited smaller plaques, slower growth kinetics, and lower RNA synthesis than the wild-type virus in a host-dependent manner, with the greatest difference in rodent cells (C3H/He and BHK-21) and the least difference in mosquito cells (C3/36). Selection of revertants of E249G virus identified a second site mutation at residue 246, which could compensate for the low replication phenotype in cell culture. These results demonstrate that distinct residues within the C-terminal tail of flavivirus NS4B are critical for viral replication. |
| doi_str_mv | 10.1016/j.virol.2006.11.012 |
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The E249G is located at the C-terminal tail of NS4B predicted to be on the cytoplasmic side of the endoplasmic reticulum membrane. The E249G substitution reduced replicon RNA synthesis. Compared with the wild-type NS4B, the E249G mutant protein exhibited a similar efficiency in evasion of interferon-β response. Recombinant E249G virus exhibited smaller plaques, slower growth kinetics, and lower RNA synthesis than the wild-type virus in a host-dependent manner, with the greatest difference in rodent cells (C3H/He and BHK-21) and the least difference in mosquito cells (C3/36). Selection of revertants of E249G virus identified a second site mutation at residue 246, which could compensate for the low replication phenotype in cell culture. These results demonstrate that distinct residues within the C-terminal tail of flavivirus NS4B are critical for viral replication.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1016/j.virol.2006.11.012</identifier><identifier>PMID: 17178141</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adaptation, Physiological ; amino acid sequences ; Animals ; Cell Line ; Female ; Flavivirus ; Flavivirus replication ; Infectious Disease ; Interferon-beta - pharmacology ; Mice ; Mice, Inbred C3H ; molecular sequence data ; Mutation ; NS4B ; RNA, Viral - biosynthesis ; structure-activity relationships ; Viral Nonstructural Proteins - genetics ; viral proteins ; virus replication ; Virus Replication - drug effects ; West Nile Fever - prevention & control ; West Nile Fever - virology ; West Nile virus ; West Nile virus - physiology</subject><ispartof>Virology (New York, N.Y.), 2007-04, Vol.361 (1), p.229-241</ispartof><rights>Elsevier Inc.</rights><rights>2006 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c567t-6ef041363db9c4f6f44fb6787015a08b30d8fea7673f73d091318d951c2133b83</citedby><cites>FETCH-LOGICAL-c567t-6ef041363db9c4f6f44fb6787015a08b30d8fea7673f73d091318d951c2133b83</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.2006.11.012$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17178141$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Puig-Basagoiti, Francesc</creatorcontrib><creatorcontrib>Tilgner, Mark</creatorcontrib><creatorcontrib>Bennett, Corey J</creatorcontrib><creatorcontrib>Zhou, Yangsheng</creatorcontrib><creatorcontrib>Muñoz-Jordán, Jorge L</creatorcontrib><creatorcontrib>García-Sastre, Adolfo</creatorcontrib><creatorcontrib>Bernard, Kristen A</creatorcontrib><creatorcontrib>Shi, Pei-Yong</creatorcontrib><title>A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis</title><title>Virology (New York, N.Y.)</title><addtitle>Virology</addtitle><description>Abstract An adaptive mutation (E249G) within West Nile virus (WNV) NS4B gene was consistently recovered from replicon RNAs in C3H/He mouse cells. The E249G is located at the C-terminal tail of NS4B predicted to be on the cytoplasmic side of the endoplasmic reticulum membrane. The E249G substitution reduced replicon RNA synthesis. Compared with the wild-type NS4B, the E249G mutant protein exhibited a similar efficiency in evasion of interferon-β response. Recombinant E249G virus exhibited smaller plaques, slower growth kinetics, and lower RNA synthesis than the wild-type virus in a host-dependent manner, with the greatest difference in rodent cells (C3H/He and BHK-21) and the least difference in mosquito cells (C3/36). Selection of revertants of E249G virus identified a second site mutation at residue 246, which could compensate for the low replication phenotype in cell culture. These results demonstrate that distinct residues within the C-terminal tail of flavivirus NS4B are critical for viral replication.</description><subject>Adaptation, Physiological</subject><subject>amino acid sequences</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Female</subject><subject>Flavivirus</subject><subject>Flavivirus replication</subject><subject>Infectious Disease</subject><subject>Interferon-beta - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>molecular sequence data</subject><subject>Mutation</subject><subject>NS4B</subject><subject>RNA, Viral - biosynthesis</subject><subject>structure-activity relationships</subject><subject>Viral Nonstructural Proteins - genetics</subject><subject>viral proteins</subject><subject>virus replication</subject><subject>Virus Replication - drug effects</subject><subject>West Nile Fever - prevention & control</subject><subject>West Nile Fever - virology</subject><subject>West Nile virus</subject><subject>West Nile virus - physiology</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>eNqFkkuP0zAQgCMEYsvCL0CCnLglzNiJnRxYqax4iVWRKCuOluNMdl3SpGs7lfrvcWjF67Iny_I345n5JkmeI-QIKF5v8r11Y58zAJEj5oDsQbJAqEUGvMCHyQKgYJmoGDtLnni_gXiXEh4nZyhRVljgIvm8TLfj5Ck11PeZbvUuUJuu1sXbdDsFHew4pDoEGiYdyKffyYd0ZXtK49-TT7-ulqk_DOGWvPVPk0ed7j09O53nyfX7d98uP2ZXXz58ulxeZaYUMmSCOiiQC942tSk60RVF1whZScBSQ9VwaKuOtBSSd5K3UCPHqq1LNAw5byp-nlwc8-6mZkutoSE43auds1vtDmrUVv37MthbdTPuFdYlY5zFBK9OCdx4N8WW1Nb6eQB6oDgMJYFXJdb8XhBrIWsEGUF-BI0bvXfU_a4GQc221Eb9sqVmWwpRRVsx6sXfjfyJOemJwMsj0OlR6RtnvbpeM0AOIKNWWUfizZGgOPC9Jae8sTQYaq0jE1Q72ntKuPgv3vR2sEb3P-hAfjNOboguFSrPFKj1vFLzRoEAqAos-U9xRsSE</recordid><startdate>20070425</startdate><enddate>20070425</enddate><creator>Puig-Basagoiti, Francesc</creator><creator>Tilgner, Mark</creator><creator>Bennett, Corey J</creator><creator>Zhou, Yangsheng</creator><creator>Muñoz-Jordán, Jorge L</creator><creator>García-Sastre, Adolfo</creator><creator>Bernard, Kristen A</creator><creator>Shi, Pei-Yong</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>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070425</creationdate><title>A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis</title><author>Puig-Basagoiti, Francesc ; Tilgner, Mark ; Bennett, Corey J ; Zhou, Yangsheng ; Muñoz-Jordán, Jorge L ; García-Sastre, Adolfo ; Bernard, Kristen A ; Shi, Pei-Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c567t-6ef041363db9c4f6f44fb6787015a08b30d8fea7673f73d091318d951c2133b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adaptation, Physiological</topic><topic>amino acid sequences</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Female</topic><topic>Flavivirus</topic><topic>Flavivirus replication</topic><topic>Infectious Disease</topic><topic>Interferon-beta - pharmacology</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>molecular sequence data</topic><topic>Mutation</topic><topic>NS4B</topic><topic>RNA, Viral - biosynthesis</topic><topic>structure-activity relationships</topic><topic>Viral Nonstructural Proteins - genetics</topic><topic>viral proteins</topic><topic>virus replication</topic><topic>Virus Replication - drug effects</topic><topic>West Nile Fever - prevention & control</topic><topic>West Nile Fever - virology</topic><topic>West Nile virus</topic><topic>West Nile virus - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Puig-Basagoiti, Francesc</creatorcontrib><creatorcontrib>Tilgner, Mark</creatorcontrib><creatorcontrib>Bennett, Corey J</creatorcontrib><creatorcontrib>Zhou, Yangsheng</creatorcontrib><creatorcontrib>Muñoz-Jordán, Jorge L</creatorcontrib><creatorcontrib>García-Sastre, Adolfo</creatorcontrib><creatorcontrib>Bernard, Kristen A</creatorcontrib><creatorcontrib>Shi, Pei-Yong</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>Nucleic Acids 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><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Virology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Puig-Basagoiti, Francesc</au><au>Tilgner, Mark</au><au>Bennett, Corey J</au><au>Zhou, Yangsheng</au><au>Muñoz-Jordán, Jorge L</au><au>García-Sastre, Adolfo</au><au>Bernard, Kristen A</au><au>Shi, Pei-Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis</atitle><jtitle>Virology (New York, N.Y.)</jtitle><addtitle>Virology</addtitle><date>2007-04-25</date><risdate>2007</risdate><volume>361</volume><issue>1</issue><spage>229</spage><epage>241</epage><pages>229-241</pages><issn>0042-6822</issn><eissn>1096-0341</eissn><abstract>Abstract An adaptive mutation (E249G) within West Nile virus (WNV) NS4B gene was consistently recovered from replicon RNAs in C3H/He mouse cells. The E249G is located at the C-terminal tail of NS4B predicted to be on the cytoplasmic side of the endoplasmic reticulum membrane. The E249G substitution reduced replicon RNA synthesis. Compared with the wild-type NS4B, the E249G mutant protein exhibited a similar efficiency in evasion of interferon-β response. Recombinant E249G virus exhibited smaller plaques, slower growth kinetics, and lower RNA synthesis than the wild-type virus in a host-dependent manner, with the greatest difference in rodent cells (C3H/He and BHK-21) and the least difference in mosquito cells (C3/36). Selection of revertants of E249G virus identified a second site mutation at residue 246, which could compensate for the low replication phenotype in cell culture. 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| ispartof | Virology (New York, N.Y.), 2007-04, Vol.361 (1), p.229-241 |
| issn | 0042-6822 1096-0341 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adaptation, Physiological amino acid sequences Animals Cell Line Female Flavivirus Flavivirus replication Infectious Disease Interferon-beta - pharmacology Mice Mice, Inbred C3H molecular sequence data Mutation NS4B RNA, Viral - biosynthesis structure-activity relationships Viral Nonstructural Proteins - genetics viral proteins virus replication Virus Replication - drug effects West Nile Fever - prevention & control West Nile Fever - virology West Nile virus West Nile virus - physiology |
| title | A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis |
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