LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells
IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for tr...
Ausführliche Beschreibung
Autor*in: |
Jingwei Zhang [verfasserIn] Thomas Sommermann [verfasserIn] Xun Li [verfasserIn] Lutz Gieselmann [verfasserIn] Kathrin de la Rosa [verfasserIn] Maria Stecklum [verfasserIn] Florian Klein [verfasserIn] Christine Kocks [verfasserIn] Klaus Rajewsky [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Übergeordnetes Werk: |
In: Frontiers in Immunology - Frontiers Media S.A., 2011, 14(2023) |
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Übergeordnetes Werk: |
volume:14 ; year:2023 |
Links: |
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DOI / URN: |
10.3389/fimmu.2023.1331730 |
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Katalog-ID: |
DOAJ099067560 |
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520 | |a IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. | ||
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650 | 4 | |a Epstein-Barr nuclear antigen 2 (EBNA2) | |
650 | 4 | |a latent membrane protein 1 (LMP1) | |
653 | 0 | |a Immunologic diseases. Allergy | |
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10.3389/fimmu.2023.1331730 doi (DE-627)DOAJ099067560 (DE-599)DOAJ8852a3cd953b41d59483648d9256e588 DE-627 ger DE-627 rakwb eng RC581-607 Jingwei Zhang verfasserin aut LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. B cell lymphoma lymphomagenesis Epstein-Barr virus (EBV) EBV latent genes Epstein-Barr nuclear antigen 2 (EBNA2) latent membrane protein 1 (LMP1) Immunologic diseases. Allergy Thomas Sommermann verfasserin aut Xun Li verfasserin aut Lutz Gieselmann verfasserin aut Lutz Gieselmann verfasserin aut Kathrin de la Rosa verfasserin aut Kathrin de la Rosa verfasserin aut Maria Stecklum verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Christine Kocks verfasserin aut Klaus Rajewsky verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1331730 kostenfrei https://doaj.org/article/8852a3cd953b41d59483648d9256e588 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1331730/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 |
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10.3389/fimmu.2023.1331730 doi (DE-627)DOAJ099067560 (DE-599)DOAJ8852a3cd953b41d59483648d9256e588 DE-627 ger DE-627 rakwb eng RC581-607 Jingwei Zhang verfasserin aut LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. B cell lymphoma lymphomagenesis Epstein-Barr virus (EBV) EBV latent genes Epstein-Barr nuclear antigen 2 (EBNA2) latent membrane protein 1 (LMP1) Immunologic diseases. Allergy Thomas Sommermann verfasserin aut Xun Li verfasserin aut Lutz Gieselmann verfasserin aut Lutz Gieselmann verfasserin aut Kathrin de la Rosa verfasserin aut Kathrin de la Rosa verfasserin aut Maria Stecklum verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Christine Kocks verfasserin aut Klaus Rajewsky verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1331730 kostenfrei https://doaj.org/article/8852a3cd953b41d59483648d9256e588 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1331730/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 |
allfields_unstemmed |
10.3389/fimmu.2023.1331730 doi (DE-627)DOAJ099067560 (DE-599)DOAJ8852a3cd953b41d59483648d9256e588 DE-627 ger DE-627 rakwb eng RC581-607 Jingwei Zhang verfasserin aut LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. B cell lymphoma lymphomagenesis Epstein-Barr virus (EBV) EBV latent genes Epstein-Barr nuclear antigen 2 (EBNA2) latent membrane protein 1 (LMP1) Immunologic diseases. Allergy Thomas Sommermann verfasserin aut Xun Li verfasserin aut Lutz Gieselmann verfasserin aut Lutz Gieselmann verfasserin aut Kathrin de la Rosa verfasserin aut Kathrin de la Rosa verfasserin aut Maria Stecklum verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Christine Kocks verfasserin aut Klaus Rajewsky verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1331730 kostenfrei https://doaj.org/article/8852a3cd953b41d59483648d9256e588 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1331730/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 |
allfieldsGer |
10.3389/fimmu.2023.1331730 doi (DE-627)DOAJ099067560 (DE-599)DOAJ8852a3cd953b41d59483648d9256e588 DE-627 ger DE-627 rakwb eng RC581-607 Jingwei Zhang verfasserin aut LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. B cell lymphoma lymphomagenesis Epstein-Barr virus (EBV) EBV latent genes Epstein-Barr nuclear antigen 2 (EBNA2) latent membrane protein 1 (LMP1) Immunologic diseases. Allergy Thomas Sommermann verfasserin aut Xun Li verfasserin aut Lutz Gieselmann verfasserin aut Lutz Gieselmann verfasserin aut Kathrin de la Rosa verfasserin aut Kathrin de la Rosa verfasserin aut Maria Stecklum verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Christine Kocks verfasserin aut Klaus Rajewsky verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1331730 kostenfrei https://doaj.org/article/8852a3cd953b41d59483648d9256e588 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1331730/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 |
allfieldsSound |
10.3389/fimmu.2023.1331730 doi (DE-627)DOAJ099067560 (DE-599)DOAJ8852a3cd953b41d59483648d9256e588 DE-627 ger DE-627 rakwb eng RC581-607 Jingwei Zhang verfasserin aut LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. B cell lymphoma lymphomagenesis Epstein-Barr virus (EBV) EBV latent genes Epstein-Barr nuclear antigen 2 (EBNA2) latent membrane protein 1 (LMP1) Immunologic diseases. Allergy Thomas Sommermann verfasserin aut Xun Li verfasserin aut Lutz Gieselmann verfasserin aut Lutz Gieselmann verfasserin aut Kathrin de la Rosa verfasserin aut Kathrin de la Rosa verfasserin aut Maria Stecklum verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Florian Klein verfasserin aut Christine Kocks verfasserin aut Klaus Rajewsky verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1331730 kostenfrei https://doaj.org/article/8852a3cd953b41d59483648d9256e588 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1331730/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ099067560</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414012230.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240414s2023 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2023.1331730</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ099067560</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ8852a3cd953b41d59483648d9256e588</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Jingwei Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. 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Jingwei Zhang misc RC581-607 misc B cell lymphoma misc lymphomagenesis misc Epstein-Barr virus (EBV) misc EBV latent genes misc Epstein-Barr nuclear antigen 2 (EBNA2) misc latent membrane protein 1 (LMP1) misc Immunologic diseases. Allergy LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells |
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RC581-607 LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells B cell lymphoma lymphomagenesis Epstein-Barr virus (EBV) EBV latent genes Epstein-Barr nuclear antigen 2 (EBNA2) latent membrane protein 1 (LMP1) |
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LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells |
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IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. |
abstractGer |
IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. |
abstract_unstemmed |
IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation. |
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LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells |
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https://doi.org/10.3389/fimmu.2023.1331730 https://doaj.org/article/8852a3cd953b41d59483648d9256e588 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1331730/full https://doaj.org/toc/1664-3224 |
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Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. 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