Jern Patric, Sperber Göran O, Ahlsén Göran, Blomberg Jonas
Section of Virology, Department of Medical Sciences, Uppsala University, Academic Hospital, Dag Hammarskjolds v. 17, SE-751 85 Uppsala, Sweden.
J Virol. 2005 May;79(10):6325-37. doi: 10.1128/JVI.79.10.6325-6337.2005.
Recently, we identified and classified 926 human endogenous retrovirus H (HERV-H)-like proviruses in the human genome. In this paper, we used the information to, in silico, reconstruct a putative ancestral HERV-H. A calculated consensus sequence was nearly open in all genes. A few manual adjustments resulted in a putative 9-kb HERV-H provirus with open reading frames (ORFs) in gag, pro, pol, and env. Long terminal repeats (LTRs) differed by 1.1%, indicating proximity to an integration event. The gag ORF was extended upstream of the normal myristylation start site. There was a long leader (including a "pre-gag" ORF) region positioned like the N terminus of murine leukemia virus (MLV) "glyco-Gag," potentially encoding a proline- and serine-rich domain remotely similar to MLV pp12. Another ORF, starting inside the 5' LTR, had no obvious similarity to known protein domains. Unlike other hitherto described gammaretroviruses, the reconstructed Gag had two zinc finger motifs. Alternative splicing of sequences related to the HERV-H consensus was confirmed using dbEST data. env transcripts were most prevalent in colon tumors, but also in normal testis. We found no evidence for full length env transcripts in the dbEST. HERV-H had a markedly skewed nucleotide composition, disfavoring guanine and favoring cytidine. We conclude that the HERV-H consensus shared a gene arrangement common to gammaretroviruses with gag separated by stop codon from pro-pol in the same reading frame, while env resides in another reading frame. There was also alternative splicing. HERV-H consensus yielded new insights in gammaretroviral evolution and will be useful as a model in studies on expression and function.
最近，我们在人类基因组中鉴定并分类了926种人类内源性逆转录病毒H（HERV-H）样原病毒。在本文中，我们利用这些信息在计算机上重建了一种假定的祖先HERV-H。计算得出的共有序列在所有基因中几乎都是开放的。经过一些人工调整，得到了一种假定的9 kb HERV-H原病毒，其在gag、pro、pol和env基因中有开放阅读框（ORF）。长末端重复序列（LTR）的差异为1.1%，表明接近整合事件。gag ORF在正常肉豆蔻酰化起始位点的上游延伸。有一个长的前导区（包括一个“前gag”ORF），其位置类似于鼠白血病病毒（MLV）“糖基化Gag”的N末端，可能编码一个与MLV pp12有远距离相似性的富含脯氨酸和丝氨酸的结构域。另一个从5' LTR内部开始的ORF与已知蛋白质结构域没有明显的相似性。与其他迄今描述的γ逆转录病毒不同，重建的Gag有两个锌指基序。利用dbEST数据证实了与HERV-H共有序列相关的序列的可变剪接。env转录本在结肠肿瘤中最为普遍，但在正常睾丸中也有。我们在dbEST中没有发现全长env转录本的证据。HERV-H的核苷酸组成明显偏向，不利于鸟嘌呤而有利于胞嘧啶。我们得出结论，HERV-H共有序列与γ逆转录病毒共享一种共同的基因排列，gag在同一阅读框中由终止密码子与pro-pol分开，而env位于另一个阅读框中。此外还有可变剪接。HERV-H共有序列为γ逆转录病毒的进化提供了新的见解，并将作为研究表达和功能的模型。
