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Novel Organizational Features, Captured Cellular Genes, and Strain Variability Within the Genome of KSHV/HHV8

Novel Organizational Features, Captured Cellular Genes, and Strain Variability Within the Genome... Strong serologic and molecular probe correlations indicate that the newly discovered gamma herpesvirus KSHV or HHV8 is the likely etiologic agent of all forms of Kaposi's sarcoma as well as BCBL/PEL and MCD in patients with acquired immunodeficiency syndrome (AIDS). Two large segments of HHV8 DNA from an AIDS-associated BCBL tumor covering genomic positions 0-52 kilobase (kb) and 108-140 kb have been cloned, mapped, and partially sequenced. Our studies have focused on novel viral proteins encoded within a 13-kb divergent locus (DL-B) by nine captured homologues of cellular genes, including vIL-6, vDHFR, vTS, vBcl-2, three C-C beta chemokines (vMIP-1A, vMIP-1B, and vBCK), and two LAP/PHD subclass zinc finger proteins (IE1A and IE1B). The HHV-8 vIL-6, vDHFR, vTS, and vBcl-2 proteins have all been shown to be active in a variety of appropriate functional assays, and transcripts from vIL-6, vMIP-1B, vIE1-A, vIE1-B, and vDHFR genes are all expressed as abundant single messenger RNA species after butyrate or phorbol ester (TPA) induction of the lytic cycle in HHV8-positive BCBL cell lines. All of these genes lie within a divergent transcriptional domain that contains a single central enhancer and associated untranslated leader region plus seven distinct proximal promoters, some of which are negatively regulated through AP-1 and ZRE motifs by the EBV ZTA transactivator. This region also encompasses a predicted complex oriLyt domain of 1050 bp that is duplicated in inverted orientation adjacent to the T0.7 latency RNA in another large divergent locus (DL-E). We have previously described three distinct subtypes of the HHV8 genome that differ by 1.0%-1.5% at the nucleotide level within the ORF26 and ORF75 genes. Certain strains or clades appear to have preferential geographic distributions, but it is not known as yet whether there are any specific disease associations. Interestingly, the A, B, and C subtypes of HHV-8 also proved to differ dramatically in coding content at both the extreme left and right ends of the unique segment of the genome as well as in the positions of the junctions with the terminal repeats. On the left-hand side, the receptor-like ORF-K1 protein is highly variable with A-strain subtypes displaying 15% amino acid differences from C strains and up to 30% differences from B strains. On the right-hand side, two unrelated alternative types of the putative multiple membrane spanning ORF-K15 protein are found. Oxford University Press « Previous | Next Article » Table of Contents This Article J Natl Cancer Inst Monogr (1998) 1998 (23): 79-88. 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Novel Organizational Features, Captured Cellular Genes, and Strain Variability Within the Genome of KSHV/HHV8

JNCI Monographs , Volume 1998 (23) – Apr 1, 1998

Abstract

Strong serologic and molecular probe correlations indicate that the newly discovered gamma herpesvirus KSHV or HHV8 is the likely etiologic agent of all forms of Kaposi's sarcoma as well as BCBL/PEL and MCD in patients with acquired immunodeficiency syndrome (AIDS). Two large segments of HHV8 DNA from an AIDS-associated BCBL tumor covering genomic positions 0-52 kilobase (kb) and 108-140 kb have been cloned, mapped, and partially sequenced. Our studies have focused on novel viral proteins encoded within a 13-kb divergent locus (DL-B) by nine captured homologues of cellular genes, including vIL-6, vDHFR, vTS, vBcl-2, three C-C beta chemokines (vMIP-1A, vMIP-1B, and vBCK), and two LAP/PHD subclass zinc finger proteins (IE1A and IE1B). The HHV-8 vIL-6, vDHFR, vTS, and vBcl-2 proteins have all been shown to be active in a variety of appropriate functional assays, and transcripts from vIL-6, vMIP-1B, vIE1-A, vIE1-B, and vDHFR genes are all expressed as abundant single messenger RNA species after butyrate or phorbol ester (TPA) induction of the lytic cycle in HHV8-positive BCBL cell lines. All of these genes lie within a divergent transcriptional domain that contains a single central enhancer and associated untranslated leader region plus seven distinct proximal promoters, some of which are negatively regulated through AP-1 and ZRE motifs by the EBV ZTA transactivator. This region also encompasses a predicted complex oriLyt domain of 1050 bp that is duplicated in inverted orientation adjacent to the T0.7 latency RNA in another large divergent locus (DL-E). We have previously described three distinct subtypes of the HHV8 genome that differ by 1.0%-1.5% at the nucleotide level within the ORF26 and ORF75 genes. Certain strains or clades appear to have preferential geographic distributions, but it is not known as yet whether there are any specific disease associations. Interestingly, the A, B, and C subtypes of HHV-8 also proved to differ dramatically in coding content at both the extreme left and right ends of the unique segment of the genome as well as in the positions of the junctions with the terminal repeats. On the left-hand side, the receptor-like ORF-K1 protein is highly variable with A-strain subtypes displaying 15% amino acid differences from C strains and up to 30% differences from B strains. On the right-hand side, two unrelated alternative types of the putative multiple membrane spanning ORF-K15 protein are found. Oxford University Press « Previous | Next Article » Table of Contents This Article J Natl Cancer Inst Monogr (1998) 1998 (23): 79-88. This article appears in: First National AIDS Malignancy Conference » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Article Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Nicholas, J. Articles by Hayward, G. S. Search for related content PubMed PubMed citation Articles by Nicholas, J. Articles by Zong, J. C. Articles by Alcendor, D. J. Articles by Ciufo, D. M. Articles by Poole, L. J. Articles by Sarisky, R. T. Articles by Chiou, C. J. Articles by Zhang, X. Articles by Wan, X. Articles by Guo, H. G. Articles by Reitz, M. S. Articles by Hayward, G. S. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue May 2015 2015 (51) Alert me to new issues The Journal About this journal Rights & Permissions We are mobile – find out more Journals Career Network Editor-in-Chief Carmen J. Allegra View the JNCI editorial board For Authors Instructions to authors Author Self Archiving Policy Alerting Services Email table of contents CiteTrack XML RSS feed Corporate Services Advertising sales Reprints var taxonomies = ("MED00300"); Most Most Read Clinical Practice Guidelines on the Use of Integrative Therapies as Supportive Care in Patients Treated for Breast Cancer Descriptive Review of the Literature on Breast Cancer Outcomes: 1990 Through 2000 Prevalence of Depression in Patients With Cancer Biology of Oral Mucosa and Esophagus Chapter 6: Estrogen Metabolism by Conjugation » View all Most Read articles Most Cited Chapter 1: Human Papillomavirus and Cervical Cancer--Burden and Assessment of Causality Chapter 4: Estrogens as Endogenous Genotoxic Agents--DNA Adducts and Mutations Prevalence of Depression in Patients With Cancer Preoperative Chemotherapy in Patients With Operable Breast Cancer: Nine-Year Results From National Surgical Adjuvant Breast and Bowel Project B-18 Overview of the Randomized Trials of Radiotherapy in Ductal Carcinoma In Situ of the Breast » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department. 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Publisher
Oxford University Press
Copyright
Copyright © 2015 Oxford University Press
ISSN
1052-6773
eISSN
1745-6614
DOI
jncimono;1998/23/79
Publisher site
See Article on Publisher Site

Abstract

Strong serologic and molecular probe correlations indicate that the newly discovered gamma herpesvirus KSHV or HHV8 is the likely etiologic agent of all forms of Kaposi's sarcoma as well as BCBL/PEL and MCD in patients with acquired immunodeficiency syndrome (AIDS). Two large segments of HHV8 DNA from an AIDS-associated BCBL tumor covering genomic positions 0-52 kilobase (kb) and 108-140 kb have been cloned, mapped, and partially sequenced. Our studies have focused on novel viral proteins encoded within a 13-kb divergent locus (DL-B) by nine captured homologues of cellular genes, including vIL-6, vDHFR, vTS, vBcl-2, three C-C beta chemokines (vMIP-1A, vMIP-1B, and vBCK), and two LAP/PHD subclass zinc finger proteins (IE1A and IE1B). The HHV-8 vIL-6, vDHFR, vTS, and vBcl-2 proteins have all been shown to be active in a variety of appropriate functional assays, and transcripts from vIL-6, vMIP-1B, vIE1-A, vIE1-B, and vDHFR genes are all expressed as abundant single messenger RNA species after butyrate or phorbol ester (TPA) induction of the lytic cycle in HHV8-positive BCBL cell lines. All of these genes lie within a divergent transcriptional domain that contains a single central enhancer and associated untranslated leader region plus seven distinct proximal promoters, some of which are negatively regulated through AP-1 and ZRE motifs by the EBV ZTA transactivator. This region also encompasses a predicted complex oriLyt domain of 1050 bp that is duplicated in inverted orientation adjacent to the T0.7 latency RNA in another large divergent locus (DL-E). We have previously described three distinct subtypes of the HHV8 genome that differ by 1.0%-1.5% at the nucleotide level within the ORF26 and ORF75 genes. Certain strains or clades appear to have preferential geographic distributions, but it is not known as yet whether there are any specific disease associations. Interestingly, the A, B, and C subtypes of HHV-8 also proved to differ dramatically in coding content at both the extreme left and right ends of the unique segment of the genome as well as in the positions of the junctions with the terminal repeats. On the left-hand side, the receptor-like ORF-K1 protein is highly variable with A-strain subtypes displaying 15% amino acid differences from C strains and up to 30% differences from B strains. On the right-hand side, two unrelated alternative types of the putative multiple membrane spanning ORF-K15 protein are found. Oxford University Press « Previous | Next Article » Table of Contents This Article J Natl Cancer Inst Monogr (1998) 1998 (23): 79-88. This article appears in: First National AIDS Malignancy Conference » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Article Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Nicholas, J. Articles by Hayward, G. S. Search for related content PubMed PubMed citation Articles by Nicholas, J. Articles by Zong, J. C. Articles by Alcendor, D. J. Articles by Ciufo, D. M. Articles by Poole, L. J. Articles by Sarisky, R. T. Articles by Chiou, C. J. Articles by Zhang, X. Articles by Wan, X. Articles by Guo, H. G. Articles by Reitz, M. S. Articles by Hayward, G. S. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue May 2015 2015 (51) Alert me to new issues The Journal About this journal Rights & Permissions We are mobile – find out more Journals Career Network Editor-in-Chief Carmen J. Allegra View the JNCI editorial board For Authors Instructions to authors Author Self Archiving Policy Alerting Services Email table of contents CiteTrack XML RSS feed Corporate Services Advertising sales Reprints var taxonomies = ("MED00300"); Most Most Read Clinical Practice Guidelines on the Use of Integrative Therapies as Supportive Care in Patients Treated for Breast Cancer Descriptive Review of the Literature on Breast Cancer Outcomes: 1990 Through 2000 Prevalence of Depression in Patients With Cancer Biology of Oral Mucosa and Esophagus Chapter 6: Estrogen Metabolism by Conjugation » View all Most Read articles Most Cited Chapter 1: Human Papillomavirus and Cervical Cancer--Burden and Assessment of Causality Chapter 4: Estrogens as Endogenous Genotoxic Agents--DNA Adducts and Mutations Prevalence of Depression in Patients With Cancer Preoperative Chemotherapy in Patients With Operable Breast Cancer: Nine-Year Results From National Surgical Adjuvant Breast and Bowel Project B-18 Overview of the Randomized Trials of Radiotherapy in Ductal Carcinoma In Situ of the Breast » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department. Online ISSN 1745-6614 - Print ISSN 1052-6773 Copyright © 2015 Oxford University Press Oxford Journals Oxford University Press Site Map Privacy Policy Cookie Policy Legal Notices Frequently Asked Questions Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan Academic & Professional books Children's & Schools Books Dictionaries & Reference Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks International Education Unit Law Medicine Music Online Products & Publishing Oxford Bibliographies Online Oxford Dictionaries Online Oxford English Dictionary Oxford Language Dictionaries Online Oxford Scholarship Online Reference Rights and Permissions Resources for Retailers & Wholesalers Resources for the Healthcare Industry Very Short Introductions World's Classics function fnc_onDomLoaded() { var query_context = getQueryContext(); PF_initOIUnderbar(query_context,":QS:default","","JRN"); PF_insertOIUnderbar(0); }; if (window.addEventListener) { window.addEventListener('load', fnc_onDomLoaded, false); } else if (window.attachEvent) { window.attachEvent('onload', fnc_onDomLoaded); } var gaJsHost = (("https:" == document.location.protocol) ? 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Journal

JNCI MonographsOxford University Press

Published: Apr 1, 1998

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