Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production
Summary The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full‐length p7 protein of the HCV‐A strain of genotype 1b (GT1b; Virology; 2...
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| Veröffentlicht in: | Journal of viral hepatitis 2013-04, Vol.20 (4), p.e66-e71 |
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| container_issue | 4 |
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| container_title | Journal of viral hepatitis |
| container_volume | 20 |
| creator | Gouklani, H. Beyer, C. Drummer, H. Gowans, E. J. Netter, H. J. Haqshenas, G. |
| description | Summary
The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full‐length p7 protein of the HCV‐A strain of genotype 1b (GT1b; Virology; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild‐type JFH1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core (K74M), NS2 (T23N, H99P) and NS5A (D251G). Forward genetic analysis demonstrated that all single mutations restored the infectivity of the defective chimeric genomes suggesting that the infectious virus production involves the association of p7 with specific regions in core, NS2 and NS5A. In addition, it was demonstrated that the NS2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT6 of HCV. |
| doi_str_mv | 10.1111/jvh.12004 |
| format | Article |
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The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full‐length p7 protein of the HCV‐A strain of genotype 1b (GT1b; Virology; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild‐type JFH1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core (K74M), NS2 (T23N, H99P) and NS5A (D251G). Forward genetic analysis demonstrated that all single mutations restored the infectivity of the defective chimeric genomes suggesting that the infectious virus production involves the association of p7 with specific regions in core, NS2 and NS5A. In addition, it was demonstrated that the NS2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT6 of HCV.</description><identifier>ISSN: 1352-0504</identifier><identifier>EISSN: 1365-2893</identifier><identifier>DOI: 10.1111/jvh.12004</identifier><identifier>PMID: 23490391</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Amino acid substitution ; core ; DNA Mutational Analysis ; Hepacivirus - genetics ; Hepacivirus - physiology ; Hepatitis ; Hepatitis C virus ; JFH1 ; morphogenesis ; NS2 ; NS5A ; Protein Interaction Domains and Motifs ; Protein Interaction Mapping ; Proteins ; Viral Core Proteins - genetics ; Viral Core Proteins - metabolism ; Viral Nonstructural Proteins - genetics ; Viral Nonstructural Proteins - metabolism ; Viral Proteins - genetics ; Viral Proteins - metabolism ; Virus Replication</subject><ispartof>Journal of viral hepatitis, 2013-04, Vol.20 (4), p.e66-e71</ispartof><rights>2012 Blackwell Publishing Ltd</rights><rights>2012 Blackwell Publishing Ltd.</rights><rights>Copyright © 2013 Blackwell Publishing Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjvh.12004$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjvh.12004$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23490391$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gouklani, H.</creatorcontrib><creatorcontrib>Beyer, C.</creatorcontrib><creatorcontrib>Drummer, H.</creatorcontrib><creatorcontrib>Gowans, E. J.</creatorcontrib><creatorcontrib>Netter, H. J.</creatorcontrib><creatorcontrib>Haqshenas, G.</creatorcontrib><title>Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production</title><title>Journal of viral hepatitis</title><addtitle>J Viral Hepat</addtitle><description>Summary
The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full‐length p7 protein of the HCV‐A strain of genotype 1b (GT1b; Virology; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild‐type JFH1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core (K74M), NS2 (T23N, H99P) and NS5A (D251G). Forward genetic analysis demonstrated that all single mutations restored the infectivity of the defective chimeric genomes suggesting that the infectious virus production involves the association of p7 with specific regions in core, NS2 and NS5A. In addition, it was demonstrated that the NS2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT6 of HCV.</description><subject>Amino acid substitution</subject><subject>core</subject><subject>DNA Mutational Analysis</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis</subject><subject>Hepatitis C virus</subject><subject>JFH1</subject><subject>morphogenesis</subject><subject>NS2</subject><subject>NS5A</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Protein Interaction Mapping</subject><subject>Proteins</subject><subject>Viral Core Proteins - genetics</subject><subject>Viral Core Proteins - metabolism</subject><subject>Viral Nonstructural Proteins - genetics</subject><subject>Viral Nonstructural Proteins - metabolism</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - metabolism</subject><subject>Virus Replication</subject><issn>1352-0504</issn><issn>1365-2893</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFO3DAQhqOqVaG0h75AZamXHhqwYzuOjyhqgYrSA7A9Wl5nwnqbTVLbAfZNeNzO7lIOnPDBM5r55h97Jss-MnrI8BwtbxeHrKBUvMr2GS9lXlSav974ssippGIvexfjklLGC8neZnsFF5pyzfazh7MG-uRb72zyQ0-GlsQR3CZAAtxgKBLfkwWMmE8-kprc-jBF4oYAX8nFZUFs36CVxyQtbCI30ENCta5bY2GCYF0idz4tyKi2qBvyITS-twkQaMFhX9TbqY5haKZNpH-fvWltF-HDoz3Irr9_u6pP8_NfJ2f18XnueSVFDng3WjDhKi2VrUrrdCOYgrYVEsWproSYs3KuhGqBNpxbxx24olAN1a3kB9mXnS62_jtBTGblo4Ousz3guwyOjFdU41hfgDJVcaUYRfTzM3Q5TKHHj2ypklGlFFKfHqlpvoLGjMGvbFib_-tB4GgH3PkO1k95Rs1m7wb3brZ7Nz9mp1sHK_JdhY8J7p8qbPhjSsWVNL8vTkxda3Y5m_00M_4Ptq6u-w</recordid><startdate>201304</startdate><enddate>201304</enddate><creator>Gouklani, H.</creator><creator>Beyer, C.</creator><creator>Drummer, H.</creator><creator>Gowans, E. J.</creator><creator>Netter, H. J.</creator><creator>Haqshenas, G.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201304</creationdate><title>Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production</title><author>Gouklani, H. ; Beyer, C. ; Drummer, H. ; Gowans, E. J. ; Netter, H. J. ; Haqshenas, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3854-e385d9414c8957a86ac9d417eff45fec09844b16b747fe0d33ac3cec227d09f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino acid substitution</topic><topic>core</topic><topic>DNA Mutational Analysis</topic><topic>Hepacivirus - genetics</topic><topic>Hepacivirus - physiology</topic><topic>Hepatitis</topic><topic>Hepatitis C virus</topic><topic>JFH1</topic><topic>morphogenesis</topic><topic>NS2</topic><topic>NS5A</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Protein Interaction Mapping</topic><topic>Proteins</topic><topic>Viral Core Proteins - genetics</topic><topic>Viral Core Proteins - metabolism</topic><topic>Viral Nonstructural Proteins - genetics</topic><topic>Viral Nonstructural Proteins - metabolism</topic><topic>Viral Proteins - genetics</topic><topic>Viral Proteins - metabolism</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gouklani, H.</creatorcontrib><creatorcontrib>Beyer, C.</creatorcontrib><creatorcontrib>Drummer, H.</creatorcontrib><creatorcontrib>Gowans, E. J.</creatorcontrib><creatorcontrib>Netter, H. J.</creatorcontrib><creatorcontrib>Haqshenas, G.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Journal of viral hepatitis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gouklani, H.</au><au>Beyer, C.</au><au>Drummer, H.</au><au>Gowans, E. J.</au><au>Netter, H. J.</au><au>Haqshenas, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production</atitle><jtitle>Journal of viral hepatitis</jtitle><addtitle>J Viral Hepat</addtitle><date>2013-04</date><risdate>2013</risdate><volume>20</volume><issue>4</issue><spage>e66</spage><epage>e71</epage><pages>e66-e71</pages><issn>1352-0504</issn><eissn>1365-2893</eissn><abstract>Summary
The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full‐length p7 protein of the HCV‐A strain of genotype 1b (GT1b; Virology; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild‐type JFH1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core (K74M), NS2 (T23N, H99P) and NS5A (D251G). Forward genetic analysis demonstrated that all single mutations restored the infectivity of the defective chimeric genomes suggesting that the infectious virus production involves the association of p7 with specific regions in core, NS2 and NS5A. In addition, it was demonstrated that the NS2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT6 of HCV.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23490391</pmid><doi>10.1111/jvh.12004</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino acid substitution core DNA Mutational Analysis Hepacivirus - genetics Hepacivirus - physiology Hepatitis Hepatitis C virus JFH1 morphogenesis NS2 NS5A Protein Interaction Domains and Motifs Protein Interaction Mapping Proteins Viral Core Proteins - genetics Viral Core Proteins - metabolism Viral Nonstructural Proteins - genetics Viral Nonstructural Proteins - metabolism Viral Proteins - genetics Viral Proteins - metabolism Virus Replication |
| title | Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production |
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