Lindner I, Ehlers B, Noack S, Dural G, Yasmum N, Bauer C, Goltz M
Robert Koch-Institut, P14 Molekulare Genetik und Epidemiologie von Herpesviren, Nordufer 20, 13353 Berlin, Germany.
Virology. 2007 Jan 20;357(2):134-48. doi: 10.1016/j.virol.2006.08.008. Epub 2006 Sep 15.
The porcine lymphotropic herpesviruses (PLHV) are discussed as possible risk factors in xenotransplantation because of the high prevalence of PLHV-1, PLHV-2 and PLHV-3 in pig populations world-wide and the fact that PLHV-1 has been found to be associated with porcine post-transplant lymphoproliferative disease. To provide structural and functional knowledge on the PLHV immediate-early (IE) transactivator genes, the central regions of the PLHV genomes were characterized by genome walking, sequence and splicing analysis. Three spliced genes were identified (ORF50, ORFA6/BZLF1(h), ORF57) encoding putative IE transactivators, homologous to (i) ORF50 and BRLF1/Rta, (ii) K8/K-bZIP and BZLF1/Zta and (iii) ORF57 and BMLF1 of HHV-8 and EBV, respectively. Expressed as myc-tag or HA-tag fusion proteins, they were located to the cellular nucleus. In reporter gene assays, several PLHV-promoters were mainly activated by PLHV-1 ORF50, to a lower level by PLHV-1 ORFA6/BZLF1(h) and not by PLHV-1 ORF57. However, the ORF57-encoded protein acted synergistically on ORF50-mediated activation.
由于猪淋巴细胞性疱疹病毒(PLHV)中的PLHV-1、PLHV-2和PLHV-3在全球猪群中普遍存在,且已发现PLHV-1与猪移植后淋巴细胞增生性疾病有关,因此它们被认为是异种移植中可能的风险因素。为了提供关于PLHV立即早期(IE)反式激活因子基因的结构和功能知识,通过基因组步移、序列和剪接分析对PLHV基因组的中心区域进行了表征。鉴定出三个剪接基因(ORF50、ORFA6/BZLF1(h)、ORF57),它们编码假定的IE反式激活因子,分别与HHV-8和EBV的(i)ORF50和BRLF1/Rta、(ii)K8/K-bZIP和BZLF1/Zta、(iii)ORF57和BMLF1同源。以myc标签或HA标签融合蛋白形式表达时,它们定位于细胞核。在报告基因检测中,几个PLHV启动子主要被PLHV-1 ORF50激活,被PLHV-1 ORFA6/BZLF1(h)激活的程度较低,而不被PLHV-1 ORF57激活。然而,ORF57编码的蛋白对ORF50介导的激活起协同作用。