Quinn G, Langford G
Imutran Limited (A Novartis Pharma AG Company), Cambridge, CB2 2YP, United Kingdom.
Virology. 2001 Jul 20;286(1):83-90. doi: 10.1006/viro.2001.0996.
Porcine endogenous retroviruses (PERV) have been shown to have zoonotic potential, both in vitro and in vivo. Once integrated into the host cell genome activation of the proviral genes is ultimately dependent upon transactivation of the long terminal repeat (LTR). Currently there is no direct evidence of host cell transcription factors interacting with PERV LTRs. Using comparative genomics we discovered a potentially functional single nucleotide polymorphism (SNP) within the U5 region downstream of the TATA box in the PERV LTR that distinguishes PERV A from PERV B and PERV C subtypes. We demonstrated that the SNP occurs within a potential hormone-responsive region where it has a profound effect, not only upon estrogen receptor binding but also upon the binding of other transcription factors at this site. These results suggest that differences in transcriptional regulation between PERV subtypes are subtle and, as for other retroviruses, transcription can be mediated by steroid hormone receptors.
猪内源性逆转录病毒(PERV)已被证明在体外和体内均具有人畜共患病潜力。一旦整合到宿主细胞基因组中,前病毒基因的激活最终依赖于长末端重复序列(LTR)的反式激活。目前尚无宿主细胞转录因子与PERV LTR相互作用的直接证据。通过比较基因组学,我们在PERV LTR中TATA框下游的U5区域发现了一个潜在功能性单核苷酸多态性(SNP),该SNP可区分PERV A与PERV B和PERV C亚型。我们证明该SNP位于一个潜在的激素反应区域内,它不仅对雌激素受体结合有深远影响,而且对该位点其他转录因子的结合也有深远影响。这些结果表明,PERV亚型之间转录调控的差异很细微,并且与其他逆转录病毒一样,转录可由类固醇激素受体介导。