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Contribution of viral recombinants to the study of the immune response against the Epstein-Barr virus
Abstract Over the past two decades, Epstein-Barr virus (EBV) mutants have become valuable tools for the analysis of viral functions. Several experimental strategies are currently used to generate recombinant mutant genomes that carry alterations in one or several viral genes. The probably most versa...
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Published in: | Seminars in cancer biology 2008-12, Vol.18 (6), p.409-415 |
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description | Abstract Over the past two decades, Epstein-Barr virus (EBV) mutants have become valuable tools for the analysis of viral functions. Several experimental strategies are currently used to generate recombinant mutant genomes that carry alterations in one or several viral genes. The probably most versatile approach utilizes bacterial artificial chromosomes (BAC) carrying parts or the whole EBV genome, which permits extensive genetic manipulations in Escherichia coli cells. The ‘mini-EBVs’, for example, which contain roughly half of the wild type viral information, efficiently transform primary B cells and have been used as gene vectors for foreign antigens. After expression in lymphoblastoid cell lines (LCLs), these antigens are efficiently presented on MHC molecules and recognized by antigen-specific T cells. These vectors, however, cannot undergo lytic replication and require a helper cell line for efficient replication and DNA packaging. Further experimental systems include the complete viral genome cloned onto a BAC. These mutants can typically be complemented by expression plasmids, some of which are expressed on EBV-derived vectors and can be propagated without requirement of a helper cell line. Over the last years, these viral recombinants have been utilized increasingly to analyse different aspects of the immune response against EBV. Immunological applications are manifold and steadily growing and include crude screening of T cell clones for their specificity towards latent versus lytic antigens, or more detailed analyses in which the exact specificity of T cells is determined using EBV mutants that lack a single viral antigen. Other applications include detailed analysis of protein domains important for immune recognition, e.g. Gly-Ala repeats in the EBV nuclear antigen 1 (EBNA1) protein, expansion of T cell clones directed against virion structures using virus-like particles and phenotypic analysis of virus mutants defective in infection. Future developments might include the genetic identification and characterization of viral proteins involved in the modulation of the immune response and, in particular, immune evasion. Recombinant viral strains are already being used experimentally for the expansion of T cells in vitro prior to in vivo cellular therapy and have been proposed as potential prophylactic vaccines. |
doi_str_mv | 10.1016/j.semcancer.2008.09.001 |
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Several experimental strategies are currently used to generate recombinant mutant genomes that carry alterations in one or several viral genes. The probably most versatile approach utilizes bacterial artificial chromosomes (BAC) carrying parts or the whole EBV genome, which permits extensive genetic manipulations in Escherichia coli cells. The ‘mini-EBVs’, for example, which contain roughly half of the wild type viral information, efficiently transform primary B cells and have been used as gene vectors for foreign antigens. After expression in lymphoblastoid cell lines (LCLs), these antigens are efficiently presented on MHC molecules and recognized by antigen-specific T cells. These vectors, however, cannot undergo lytic replication and require a helper cell line for efficient replication and DNA packaging. Further experimental systems include the complete viral genome cloned onto a BAC. These mutants can typically be complemented by expression plasmids, some of which are expressed on EBV-derived vectors and can be propagated without requirement of a helper cell line. Over the last years, these viral recombinants have been utilized increasingly to analyse different aspects of the immune response against EBV. Immunological applications are manifold and steadily growing and include crude screening of T cell clones for their specificity towards latent versus lytic antigens, or more detailed analyses in which the exact specificity of T cells is determined using EBV mutants that lack a single viral antigen. Other applications include detailed analysis of protein domains important for immune recognition, e.g. Gly-Ala repeats in the EBV nuclear antigen 1 (EBNA1) protein, expansion of T cell clones directed against virion structures using virus-like particles and phenotypic analysis of virus mutants defective in infection. Future developments might include the genetic identification and characterization of viral proteins involved in the modulation of the immune response and, in particular, immune evasion. Recombinant viral strains are already being used experimentally for the expansion of T cells in vitro prior to in vivo cellular therapy and have been proposed as potential prophylactic vaccines.</description><identifier>ISSN: 1044-579X</identifier><identifier>EISSN: 1096-3650</identifier><identifier>DOI: 10.1016/j.semcancer.2008.09.001</identifier><identifier>PMID: 18938248</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Antigens, Viral - immunology ; Antigens, Viral - metabolism ; Epstein-Barr virus ; Epstein-Barr Virus Infections - immunology ; Epstein-Barr Virus Infections - virology ; Escherichia coli ; Genetic analysis ; Genetic Vectors - genetics ; Genome, Viral - genetics ; Genome, Viral - immunology ; Hematology, Oncology and Palliative Medicine ; Herpesvirus 4, Human - genetics ; Herpesvirus 4, Human - immunology ; Humans ; Immune response ; Plasmids - genetics ; Recombinant Proteins - immunology ; Recombinant Proteins - metabolism ; T cells ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - virology ; Viral Vaccines - immunology</subject><ispartof>Seminars in cancer biology, 2008-12, Vol.18 (6), p.409-415</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-bf62f41cd5c1aed2e0bbb95b060eb03744995cb6b38c0f2487ad7e52c5260e873</citedby><cites>FETCH-LOGICAL-c455t-bf62f41cd5c1aed2e0bbb95b060eb03744995cb6b38c0f2487ad7e52c5260e873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18938248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Delecluse, Henri-Jacques</creatorcontrib><creatorcontrib>Feederle, Regina</creatorcontrib><creatorcontrib>Behrends, Uta</creatorcontrib><creatorcontrib>Mautner, Josef</creatorcontrib><title>Contribution of viral recombinants to the study of the immune response against the Epstein-Barr virus</title><title>Seminars in cancer biology</title><addtitle>Semin Cancer Biol</addtitle><description>Abstract Over the past two decades, Epstein-Barr virus (EBV) mutants have become valuable tools for the analysis of viral functions. Several experimental strategies are currently used to generate recombinant mutant genomes that carry alterations in one or several viral genes. The probably most versatile approach utilizes bacterial artificial chromosomes (BAC) carrying parts or the whole EBV genome, which permits extensive genetic manipulations in Escherichia coli cells. The ‘mini-EBVs’, for example, which contain roughly half of the wild type viral information, efficiently transform primary B cells and have been used as gene vectors for foreign antigens. After expression in lymphoblastoid cell lines (LCLs), these antigens are efficiently presented on MHC molecules and recognized by antigen-specific T cells. These vectors, however, cannot undergo lytic replication and require a helper cell line for efficient replication and DNA packaging. Further experimental systems include the complete viral genome cloned onto a BAC. These mutants can typically be complemented by expression plasmids, some of which are expressed on EBV-derived vectors and can be propagated without requirement of a helper cell line. Over the last years, these viral recombinants have been utilized increasingly to analyse different aspects of the immune response against EBV. Immunological applications are manifold and steadily growing and include crude screening of T cell clones for their specificity towards latent versus lytic antigens, or more detailed analyses in which the exact specificity of T cells is determined using EBV mutants that lack a single viral antigen. Other applications include detailed analysis of protein domains important for immune recognition, e.g. Gly-Ala repeats in the EBV nuclear antigen 1 (EBNA1) protein, expansion of T cell clones directed against virion structures using virus-like particles and phenotypic analysis of virus mutants defective in infection. Future developments might include the genetic identification and characterization of viral proteins involved in the modulation of the immune response and, in particular, immune evasion. Recombinant viral strains are already being used experimentally for the expansion of T cells in vitro prior to in vivo cellular therapy and have been proposed as potential prophylactic vaccines.</description><subject>Antigens, Viral - immunology</subject><subject>Antigens, Viral - metabolism</subject><subject>Epstein-Barr virus</subject><subject>Epstein-Barr Virus Infections - immunology</subject><subject>Epstein-Barr Virus Infections - virology</subject><subject>Escherichia coli</subject><subject>Genetic analysis</subject><subject>Genetic Vectors - genetics</subject><subject>Genome, Viral - genetics</subject><subject>Genome, Viral - immunology</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Herpesvirus 4, Human - genetics</subject><subject>Herpesvirus 4, Human - immunology</subject><subject>Humans</subject><subject>Immune response</subject><subject>Plasmids - genetics</subject><subject>Recombinant Proteins - immunology</subject><subject>Recombinant Proteins - metabolism</subject><subject>T cells</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - virology</subject><subject>Viral Vaccines - immunology</subject><issn>1044-579X</issn><issn>1096-3650</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqNkkFv1DAQhSMEoqXwFyAnbgnjxE7iC1JZtYBUiQMgcbNsZwJeEnvxOJX23-OwK5C4wMm2_M2b0XtTFC8Y1AxY92pfEy5We4uxbgCGGmQNwB4UlwxkV7WdgIfbnfNK9PLLRfGEaA8AkjP-uLhgg2yHhg-XBe6CT9GZNbngyzCV9y7quYxow2Kc1z5RmUKZvmFJaR2PG7I93LKsHjNHh-AJS_1VO0_p19_NgRI6X73RMW56Kz0tHk16Jnx2Pq-Kz7c3n3bvqrsPb9_vru8qy4VIlZm6ZuLMjsIyjWODYIyRwkAHaKDtOZdSWNOZdrAw5fl7PfYoGiuaTAx9e1W8POkeYvixIiW1OLI4z9pjWEl1cuizCc0_QSY7KYCJDPYn0MZAFHFSh-gWHY-KgdqiUHv1Owq1RaFAqhxFrnx-brGaBcc_dWfvM3B9AjA7cu9yOVmHWWd02f6kxuD-o8nrvzTs7Lyzev6OR6R9WKPPhiumqFGgPm4bsS0EDHkZet61PwH19LVR</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Delecluse, Henri-Jacques</creator><creator>Feederle, Regina</creator><creator>Behrends, Uta</creator><creator>Mautner, Josef</creator><general>Elsevier Ltd</general><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>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20081201</creationdate><title>Contribution of viral recombinants to the study of the immune response against the Epstein-Barr virus</title><author>Delecluse, Henri-Jacques ; Feederle, Regina ; Behrends, Uta ; Mautner, Josef</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-bf62f41cd5c1aed2e0bbb95b060eb03744995cb6b38c0f2487ad7e52c5260e873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antigens, Viral - immunology</topic><topic>Antigens, Viral - metabolism</topic><topic>Epstein-Barr virus</topic><topic>Epstein-Barr Virus Infections - immunology</topic><topic>Epstein-Barr Virus Infections - virology</topic><topic>Escherichia coli</topic><topic>Genetic analysis</topic><topic>Genetic Vectors - genetics</topic><topic>Genome, Viral - genetics</topic><topic>Genome, Viral - immunology</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Herpesvirus 4, Human - genetics</topic><topic>Herpesvirus 4, Human - immunology</topic><topic>Humans</topic><topic>Immune response</topic><topic>Plasmids - genetics</topic><topic>Recombinant Proteins - immunology</topic><topic>Recombinant Proteins - metabolism</topic><topic>T cells</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - virology</topic><topic>Viral Vaccines - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Delecluse, Henri-Jacques</creatorcontrib><creatorcontrib>Feederle, Regina</creatorcontrib><creatorcontrib>Behrends, Uta</creatorcontrib><creatorcontrib>Mautner, Josef</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</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><jtitle>Seminars in cancer biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Delecluse, Henri-Jacques</au><au>Feederle, Regina</au><au>Behrends, Uta</au><au>Mautner, Josef</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contribution of viral recombinants to the study of the immune response against the Epstein-Barr virus</atitle><jtitle>Seminars in cancer biology</jtitle><addtitle>Semin Cancer Biol</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>18</volume><issue>6</issue><spage>409</spage><epage>415</epage><pages>409-415</pages><issn>1044-579X</issn><eissn>1096-3650</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>ObjectType-Article-2</notes><notes>ObjectType-Feature-3</notes><notes>ObjectType-Review-1</notes><abstract>Abstract Over the past two decades, Epstein-Barr virus (EBV) mutants have become valuable tools for the analysis of viral functions. Several experimental strategies are currently used to generate recombinant mutant genomes that carry alterations in one or several viral genes. The probably most versatile approach utilizes bacterial artificial chromosomes (BAC) carrying parts or the whole EBV genome, which permits extensive genetic manipulations in Escherichia coli cells. The ‘mini-EBVs’, for example, which contain roughly half of the wild type viral information, efficiently transform primary B cells and have been used as gene vectors for foreign antigens. After expression in lymphoblastoid cell lines (LCLs), these antigens are efficiently presented on MHC molecules and recognized by antigen-specific T cells. These vectors, however, cannot undergo lytic replication and require a helper cell line for efficient replication and DNA packaging. Further experimental systems include the complete viral genome cloned onto a BAC. These mutants can typically be complemented by expression plasmids, some of which are expressed on EBV-derived vectors and can be propagated without requirement of a helper cell line. Over the last years, these viral recombinants have been utilized increasingly to analyse different aspects of the immune response against EBV. Immunological applications are manifold and steadily growing and include crude screening of T cell clones for their specificity towards latent versus lytic antigens, or more detailed analyses in which the exact specificity of T cells is determined using EBV mutants that lack a single viral antigen. Other applications include detailed analysis of protein domains important for immune recognition, e.g. Gly-Ala repeats in the EBV nuclear antigen 1 (EBNA1) protein, expansion of T cell clones directed against virion structures using virus-like particles and phenotypic analysis of virus mutants defective in infection. Future developments might include the genetic identification and characterization of viral proteins involved in the modulation of the immune response and, in particular, immune evasion. Recombinant viral strains are already being used experimentally for the expansion of T cells in vitro prior to in vivo cellular therapy and have been proposed as potential prophylactic vaccines.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>18938248</pmid><doi>10.1016/j.semcancer.2008.09.001</doi><tpages>7</tpages></addata></record> |
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subjects | Antigens, Viral - immunology Antigens, Viral - metabolism Epstein-Barr virus Epstein-Barr Virus Infections - immunology Epstein-Barr Virus Infections - virology Escherichia coli Genetic analysis Genetic Vectors - genetics Genome, Viral - genetics Genome, Viral - immunology Hematology, Oncology and Palliative Medicine Herpesvirus 4, Human - genetics Herpesvirus 4, Human - immunology Humans Immune response Plasmids - genetics Recombinant Proteins - immunology Recombinant Proteins - metabolism T cells T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - virology Viral Vaccines - immunology |
title | Contribution of viral recombinants to the study of the immune response against the Epstein-Barr virus |
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