Comparative analysis of the expression of the epstein-barr virus (EBV) anti-apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid diseases
Epstein‐Barr virus (EBV) has been identified in a wide range of neoplastic and non‐neoplastic disorders. The EBV open reading frame BHRF1 encodes a protein with partial sequence and functional homology to the anti‐apoptotic onco‐protein Bcl‐2 and may therefore have a role in the proliferation of EBV...
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| creator | Nicholls, John Kremmer, Elisabeth Meseda, Clement A. Mackett, Mike Hahn, Peter Gulley, Margaret L. Brink, Antoinette Swinnen, Lode J. Greenspan, John De Souza, Yvonne Grässer, Friedrich Sham, Jonathan Ng, Mun-Hon Arrand, John R. |
| description | Epstein‐Barr virus (EBV) has been identified in a wide range of neoplastic and non‐neoplastic disorders. The EBV open reading frame BHRF1 encodes a protein with partial sequence and functional homology to the anti‐apoptotic onco‐protein Bcl‐2 and may therefore have a role in the proliferation of EBV positive cells. We have developed a rat monoclonal antibody against pBHRF1, which can detect BHRF1 in paraffin sections. While a number of mutant versions of BHRF1 were recognised, the monoclonal did not detect the BHRF1 homologue encoded by Herpesvirus papio or two mutants with deletions in the BH2 region. This novel rat monoclonal antibody (6A9) was used to examine tissue sections from 39 cases of non‐keratinising undifferentiated nasopharyngeal carcinoma (NPC), 6 cases of metastatic NPC, 7 cases of EBV‐positive NPC with squamous differentiation from Chinese patients, 15 cases of EBV‐positive post‐transplant lymphoproliferative disorder (PTLD), 6 EBV‐containing lymphoblastoid cell lines, and 2 cases of oral hairy leukoplakia (OHL). In 11 cases of undifferentiated NPC, RT‐PCR data were available for comparison with the immunohistochemistry. Both cases of OHL and two cases of LCL were positive for BHRF1 but none of the PTLD showed positive staining. All cases of undifferentiated NPC were positive for Bcl‐2 but only one BHRF1 positive cell was identified in 1 of 39 cases of primary undifferentiated NPC. The 6A9 antibody produced less background staining and no nuclear positivity compared with the commercially available mouse monoclonal 5B11. It is concluded that BHRF1 can not be detected by immunohistochemistry in NPC and therefore it appears not to play a significant anti‐apoptotic role in the progression of this EBV‐associated tumour. The 6A9 monoclonal appears to be superior to 5B11 for the detection of pBHRF1 in tissue sections. J. Med. Virol. 65:105–113, 2001. © 2001 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jmv.2008 |
| format | Article |
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The EBV open reading frame BHRF1 encodes a protein with partial sequence and functional homology to the anti‐apoptotic onco‐protein Bcl‐2 and may therefore have a role in the proliferation of EBV positive cells. We have developed a rat monoclonal antibody against pBHRF1, which can detect BHRF1 in paraffin sections. While a number of mutant versions of BHRF1 were recognised, the monoclonal did not detect the BHRF1 homologue encoded by Herpesvirus papio or two mutants with deletions in the BH2 region. This novel rat monoclonal antibody (6A9) was used to examine tissue sections from 39 cases of non‐keratinising undifferentiated nasopharyngeal carcinoma (NPC), 6 cases of metastatic NPC, 7 cases of EBV‐positive NPC with squamous differentiation from Chinese patients, 15 cases of EBV‐positive post‐transplant lymphoproliferative disorder (PTLD), 6 EBV‐containing lymphoblastoid cell lines, and 2 cases of oral hairy leukoplakia (OHL). In 11 cases of undifferentiated NPC, RT‐PCR data were available for comparison with the immunohistochemistry. Both cases of OHL and two cases of LCL were positive for BHRF1 but none of the PTLD showed positive staining. All cases of undifferentiated NPC were positive for Bcl‐2 but only one BHRF1 positive cell was identified in 1 of 39 cases of primary undifferentiated NPC. The 6A9 antibody produced less background staining and no nuclear positivity compared with the commercially available mouse monoclonal 5B11. It is concluded that BHRF1 can not be detected by immunohistochemistry in NPC and therefore it appears not to play a significant anti‐apoptotic role in the progression of this EBV‐associated tumour. The 6A9 monoclonal appears to be superior to 5B11 for the detection of pBHRF1 in tissue sections. J. Med. Virol. 65:105–113, 2001. © 2001 Wiley‐Liss, Inc.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.2008</identifier><identifier>PMID: 11505451</identifier><identifier>CODEN: JMVIDB</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Inc</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies, Monoclonal - immunology ; Antibody Specificity ; apoptosis ; Apoptosis - physiology ; Bcl-2 ; BHRF1 ; BHRF1 gene ; Biological and medical sciences ; Blotting, Western ; Cell Line, Transformed ; Cell Transformation, Viral ; Epstein-Barr virus ; Epstein-Barr Virus Infections - virology ; Formaldehyde ; Fundamental and applied biological sciences. Psychology ; Herpesvirus 4, Human - metabolism ; Humans ; Immunohistochemistry ; Leukoplakia, Hairy - virology ; Lymphoproliferative Disorders - virology ; Mice ; Microbiology ; Molecular Sequence Data ; nasopharyngeal carcinoma ; Nasopharyngeal Neoplasms - virology ; oral hairy leukoplakia ; Paraffin Embedding ; post-transplant lymphoproliferative disorder ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Fixation ; Viral Proteins - chemistry ; Viral Proteins - genetics ; Viral Proteins - immunology ; Viral Proteins - metabolism</subject><ispartof>Journal of medical virology, 2001-09, Vol.65 (1), p.105-113</ispartof><rights>Copyright © 2001 Wiley‐Liss, Inc.</rights><rights>2002 INIST-CNRS</rights><rights>Copyright 2001 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4168-99b53090d5dd831393ac7e8f1807783669efa9303200af14590558aa85abc9433</citedby><cites>FETCH-LOGICAL-c4168-99b53090d5dd831393ac7e8f1807783669efa9303200af14590558aa85abc9433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.2008$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.2008$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14164450$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11505451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nicholls, John</creatorcontrib><creatorcontrib>Kremmer, Elisabeth</creatorcontrib><creatorcontrib>Meseda, Clement A.</creatorcontrib><creatorcontrib>Mackett, Mike</creatorcontrib><creatorcontrib>Hahn, Peter</creatorcontrib><creatorcontrib>Gulley, Margaret L.</creatorcontrib><creatorcontrib>Brink, Antoinette</creatorcontrib><creatorcontrib>Swinnen, Lode J.</creatorcontrib><creatorcontrib>Greenspan, John</creatorcontrib><creatorcontrib>De Souza, Yvonne</creatorcontrib><creatorcontrib>Grässer, Friedrich</creatorcontrib><creatorcontrib>Sham, Jonathan</creatorcontrib><creatorcontrib>Ng, Mun-Hon</creatorcontrib><creatorcontrib>Arrand, John R.</creatorcontrib><title>Comparative analysis of the expression of the epstein-barr virus (EBV) anti-apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid diseases</title><title>Journal of medical virology</title><addtitle>J. Med. Virol</addtitle><description>Epstein‐Barr virus (EBV) has been identified in a wide range of neoplastic and non‐neoplastic disorders. The EBV open reading frame BHRF1 encodes a protein with partial sequence and functional homology to the anti‐apoptotic onco‐protein Bcl‐2 and may therefore have a role in the proliferation of EBV positive cells. We have developed a rat monoclonal antibody against pBHRF1, which can detect BHRF1 in paraffin sections. While a number of mutant versions of BHRF1 were recognised, the monoclonal did not detect the BHRF1 homologue encoded by Herpesvirus papio or two mutants with deletions in the BH2 region. This novel rat monoclonal antibody (6A9) was used to examine tissue sections from 39 cases of non‐keratinising undifferentiated nasopharyngeal carcinoma (NPC), 6 cases of metastatic NPC, 7 cases of EBV‐positive NPC with squamous differentiation from Chinese patients, 15 cases of EBV‐positive post‐transplant lymphoproliferative disorder (PTLD), 6 EBV‐containing lymphoblastoid cell lines, and 2 cases of oral hairy leukoplakia (OHL). In 11 cases of undifferentiated NPC, RT‐PCR data were available for comparison with the immunohistochemistry. Both cases of OHL and two cases of LCL were positive for BHRF1 but none of the PTLD showed positive staining. All cases of undifferentiated NPC were positive for Bcl‐2 but only one BHRF1 positive cell was identified in 1 of 39 cases of primary undifferentiated NPC. The 6A9 antibody produced less background staining and no nuclear positivity compared with the commercially available mouse monoclonal 5B11. It is concluded that BHRF1 can not be detected by immunohistochemistry in NPC and therefore it appears not to play a significant anti‐apoptotic role in the progression of this EBV‐associated tumour. The 6A9 monoclonal appears to be superior to 5B11 for the detection of pBHRF1 in tissue sections. J. Med. Virol. 65:105–113, 2001. © 2001 Wiley‐Liss, Inc.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibody Specificity</subject><subject>apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Bcl-2</subject><subject>BHRF1</subject><subject>BHRF1 gene</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell Line, Transformed</subject><subject>Cell Transformation, Viral</subject><subject>Epstein-Barr virus</subject><subject>Epstein-Barr Virus Infections - virology</subject><subject>Formaldehyde</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Herpesvirus 4, Human - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Leukoplakia, Hairy - virology</subject><subject>Lymphoproliferative Disorders - virology</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Molecular Sequence Data</subject><subject>nasopharyngeal carcinoma</subject><subject>Nasopharyngeal Neoplasms - virology</subject><subject>oral hairy leukoplakia</subject><subject>Paraffin Embedding</subject><subject>post-transplant lymphoproliferative disorder</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tissue Fixation</subject><subject>Viral Proteins - chemistry</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - immunology</subject><subject>Viral Proteins - metabolism</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0c9u1DAQBnALgehSkHgC5AuoHFLsOE7sI126XVApEn-KxMWaTSZdl8QOdnbpvgzPiquN2hPiZMn6zYz0fYQ85-yYM5a_ue63xzlj6gGZcabLTLOKPyQzxosyK0suD8iTGK9ZEjrPH5MDziWTheQz8mfu-wECjHaLFBx0u2gj9S0d10jxZggYo_Xu7meII1qXrSAEurVhE-nR6cnl6zQ62gwGP4x-tDW9Qof0ZPl5wal11EH0wxrCzl0hdLSGUFvne0hTDU3jWcAORmxot-uHtbcNbWxEiBifkkctdBGfTe8h-bY4_TpfZuefzt7P355ndcFLlWm9koJp1simUYILLaCuULVcsapSoiw1tqAFEykkaHkhNZNSASgJq1oXQhySV_u9Q_C_NhhH09tYY9eBQ7-Jpkqxcpmr_8J0UatKygSP9rAOPsaArRmC7VMGhjNzW5pJpZnb0hJ9Me3crHps7uHUUgIvJwCxhq4N4Gob713KoCgkSy7bu9-2w90_D5oPHy-nw5O3qdWbOw_hpykrUUnz_eLMqB_Fl-U7dWEW4i8tK7zO</recordid><startdate>200109</startdate><enddate>200109</enddate><creator>Nicholls, John</creator><creator>Kremmer, Elisabeth</creator><creator>Meseda, Clement A.</creator><creator>Mackett, Mike</creator><creator>Hahn, Peter</creator><creator>Gulley, Margaret L.</creator><creator>Brink, Antoinette</creator><creator>Swinnen, Lode J.</creator><creator>Greenspan, John</creator><creator>De Souza, Yvonne</creator><creator>Grässer, Friedrich</creator><creator>Sham, Jonathan</creator><creator>Ng, Mun-Hon</creator><creator>Arrand, John R.</creator><general>John Wiley & Sons, Inc</general><general>Wiley-Liss</general><scope>BSCLL</scope><scope>IQODW</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>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200109</creationdate><title>Comparative analysis of the expression of the epstein-barr virus (EBV) anti-apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid diseases</title><author>Nicholls, John ; Kremmer, Elisabeth ; Meseda, Clement A. ; Mackett, Mike ; Hahn, Peter ; Gulley, Margaret L. ; Brink, Antoinette ; Swinnen, Lode J. ; Greenspan, John ; De Souza, Yvonne ; Grässer, Friedrich ; Sham, Jonathan ; Ng, Mun-Hon ; Arrand, John R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4168-99b53090d5dd831393ac7e8f1807783669efa9303200af14590558aa85abc9433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibody Specificity</topic><topic>apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Bcl-2</topic><topic>BHRF1</topic><topic>BHRF1 gene</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell Line, Transformed</topic><topic>Cell Transformation, Viral</topic><topic>Epstein-Barr virus</topic><topic>Epstein-Barr Virus Infections - virology</topic><topic>Formaldehyde</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Herpesvirus 4, Human - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Leukoplakia, Hairy - virology</topic><topic>Lymphoproliferative Disorders - virology</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Molecular Sequence Data</topic><topic>nasopharyngeal carcinoma</topic><topic>Nasopharyngeal Neoplasms - virology</topic><topic>oral hairy leukoplakia</topic><topic>Paraffin Embedding</topic><topic>post-transplant lymphoproliferative disorder</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tissue Fixation</topic><topic>Viral Proteins - chemistry</topic><topic>Viral Proteins - genetics</topic><topic>Viral Proteins - immunology</topic><topic>Viral Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nicholls, John</creatorcontrib><creatorcontrib>Kremmer, Elisabeth</creatorcontrib><creatorcontrib>Meseda, Clement A.</creatorcontrib><creatorcontrib>Mackett, Mike</creatorcontrib><creatorcontrib>Hahn, Peter</creatorcontrib><creatorcontrib>Gulley, Margaret L.</creatorcontrib><creatorcontrib>Brink, Antoinette</creatorcontrib><creatorcontrib>Swinnen, Lode J.</creatorcontrib><creatorcontrib>Greenspan, John</creatorcontrib><creatorcontrib>De Souza, Yvonne</creatorcontrib><creatorcontrib>Grässer, Friedrich</creatorcontrib><creatorcontrib>Sham, Jonathan</creatorcontrib><creatorcontrib>Ng, Mun-Hon</creatorcontrib><creatorcontrib>Arrand, John R.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nicholls, John</au><au>Kremmer, Elisabeth</au><au>Meseda, Clement A.</au><au>Mackett, Mike</au><au>Hahn, Peter</au><au>Gulley, Margaret L.</au><au>Brink, Antoinette</au><au>Swinnen, Lode J.</au><au>Greenspan, John</au><au>De Souza, Yvonne</au><au>Grässer, Friedrich</au><au>Sham, Jonathan</au><au>Ng, Mun-Hon</au><au>Arrand, John R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative analysis of the expression of the epstein-barr virus (EBV) anti-apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid diseases</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J. Med. Virol</addtitle><date>2001-09</date><risdate>2001</risdate><volume>65</volume><issue>1</issue><spage>105</spage><epage>113</epage><pages>105-113</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><coden>JMVIDB</coden><abstract>Epstein‐Barr virus (EBV) has been identified in a wide range of neoplastic and non‐neoplastic disorders. The EBV open reading frame BHRF1 encodes a protein with partial sequence and functional homology to the anti‐apoptotic onco‐protein Bcl‐2 and may therefore have a role in the proliferation of EBV positive cells. We have developed a rat monoclonal antibody against pBHRF1, which can detect BHRF1 in paraffin sections. While a number of mutant versions of BHRF1 were recognised, the monoclonal did not detect the BHRF1 homologue encoded by Herpesvirus papio or two mutants with deletions in the BH2 region. This novel rat monoclonal antibody (6A9) was used to examine tissue sections from 39 cases of non‐keratinising undifferentiated nasopharyngeal carcinoma (NPC), 6 cases of metastatic NPC, 7 cases of EBV‐positive NPC with squamous differentiation from Chinese patients, 15 cases of EBV‐positive post‐transplant lymphoproliferative disorder (PTLD), 6 EBV‐containing lymphoblastoid cell lines, and 2 cases of oral hairy leukoplakia (OHL). In 11 cases of undifferentiated NPC, RT‐PCR data were available for comparison with the immunohistochemistry. Both cases of OHL and two cases of LCL were positive for BHRF1 but none of the PTLD showed positive staining. All cases of undifferentiated NPC were positive for Bcl‐2 but only one BHRF1 positive cell was identified in 1 of 39 cases of primary undifferentiated NPC. The 6A9 antibody produced less background staining and no nuclear positivity compared with the commercially available mouse monoclonal 5B11. It is concluded that BHRF1 can not be detected by immunohistochemistry in NPC and therefore it appears not to play a significant anti‐apoptotic role in the progression of this EBV‐associated tumour. The 6A9 monoclonal appears to be superior to 5B11 for the detection of pBHRF1 in tissue sections. J. Med. Virol. 65:105–113, 2001. © 2001 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>John Wiley & Sons, Inc</pub><pmid>11505451</pmid><doi>10.1002/jmv.2008</doi><tpages>9</tpages></addata></record> |
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| subjects | Amino Acid Sequence Animals Antibodies, Monoclonal - immunology Antibody Specificity apoptosis Apoptosis - physiology Bcl-2 BHRF1 BHRF1 gene Biological and medical sciences Blotting, Western Cell Line, Transformed Cell Transformation, Viral Epstein-Barr virus Epstein-Barr Virus Infections - virology Formaldehyde Fundamental and applied biological sciences. Psychology Herpesvirus 4, Human - metabolism Humans Immunohistochemistry Leukoplakia, Hairy - virology Lymphoproliferative Disorders - virology Mice Microbiology Molecular Sequence Data nasopharyngeal carcinoma Nasopharyngeal Neoplasms - virology oral hairy leukoplakia Paraffin Embedding post-transplant lymphoproliferative disorder Reverse Transcriptase Polymerase Chain Reaction Tissue Fixation Viral Proteins - chemistry Viral Proteins - genetics Viral Proteins - immunology Viral Proteins - metabolism |
| title | Comparative analysis of the expression of the epstein-barr virus (EBV) anti-apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid diseases |
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