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

作者：John Nicholas, Jian Zong, Donald J. Alcendor, D M Ciufo, Lynn Poole, Robert T. Sarisky, C.-J. Chiou, X. Zhang, X. Steven Wan, H.-G. Guo, M S Reitz, Gary S. Hayward · 发表于：JNCI Monographs · 年份：1998 · DOI：10.1093/oxfordjournals.jncimonographs.a024179 · 被引用次数：149 · 研究领域：Viral-associated cancers and disorders、Cytomegalovirus and herpesvirus research、Parvovirus B19 Infection Studies

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 orientati...