Becher P, Orlich M, Thiel H J
Institut für Virologie (FB Veterinärmedizin), Justus-Liebig-Universität, D-35392 Giessen, Germany.
J Virol. 1998 Jun;72(6):5165-73. doi: 10.1128/JVI.72.6.5165-5173.1998.
The genus Pestivirus of the family Flaviviridae comprises three established species, namely, bovine viral diarrhea virus (BVDV), classical swine fever virus (CSFV), and border disease virus from sheep (BDV). In this study, we report the first complete nucleotide sequence of BDV, that of strain X818. The genome is 12,333 nucleotides long and contains one long open reading frame encoding 3, 895 amino acids. The 5' noncoding region (NCR) of BDV X818 consists of 372 nucleotides and is thus similar in length to the 5' NCR reported for other pestiviruses. The 3' NCR of X818 is 273 nucleotides long and thereby at least 32 nucleotides longer than the 3' NCR of pestiviruses analyzed thus far. Within the 3' NCR of BDV X818, the sequence motif TATTTATTTA was identified at four locations. The same repeat was found at two or three locations within the 3' NCR of different CSFV isolates but was absent in the 3' NCR of BVDV. Analysis of five additional BDV strains showed that the 3' NCR sequences are highly conserved within this species. Comparison of the deduced amino acid sequence of X818 with the ones of other pestiviruses allowed the prediction of polyprotein cleavage sites which were conserved with regard to the structural proteins. It has been reported for two BVDV strains that cleavage at the nonstructural (NS) protein sites 3/4A, 4A/4B, 4B/5A, and 5A/5B is mediated by the NS3 serine protease and for each site a conserved leucine was found at the P1 position followed by either serine or alanine at P1' (N. Tautz, K. Elbers, D. Stoll, G. Meyers, and H.-J. Thiel, J. Virol. 71:5415-5422, 1997; J. Xu, E. Mendez, P. R. Caron, C. Lin, M. A. Murcko, M. S. Collett, and C. M. Rice, J. Virol. 71:5312-5322). Interestingly, P1' of the predicted NS5A/5B cleavage site of BDV is represented by an asparagine residue. Transient expression studies demonstrated that this unusual NS5A/5B processing site is efficiently cleaved by the NS3 serine protease of BDV.
黄病毒科瘟病毒属包含三个已确定的种，即牛病毒性腹泻病毒（BVDV）、经典猪瘟病毒（CSFV）和绵羊边界病病毒（BDV）。在本研究中，我们报告了BDV X818株的首个完整核苷酸序列。该基因组长度为12333个核苷酸，包含一个编码3895个氨基酸的长开放阅读框。BDV X818的5'非编码区（NCR）由372个核苷酸组成，因此长度与其他瘟病毒报道的5' NCR相似。X818的3' NCR长273个核苷酸，因此比迄今分析的瘟病毒的3' NCR至少长32个核苷酸。在BDV X818的3' NCR内，在四个位置鉴定到序列基序TATTTATTTA。在不同CSFV分离株的3' NCR内的两个或三个位置发现了相同的重复序列，但在BVDV的3' NCR中不存在。对另外五个BDV株的分析表明，该种内的3' NCR序列高度保守。将X818推导的氨基酸序列与其他瘟病毒的序列进行比较，可预测多蛋白切割位点，这些位点在结构蛋白方面是保守的。已有报道称，对于两个BVDV株，非结构（NS）蛋白位点3/4A、4A/4B、4B/5A和5A/5B的切割由NS3丝氨酸蛋白酶介导，并且在每个位点的P1位置发现一个保守的亮氨酸，随后在P1'位置为丝氨酸或丙氨酸（N. Tautz、K. Elbers、D. Stoll、G. Meyers和H.-J. Thiel，《病毒学杂志》71:5415 - 5422，1997；J. Xu、E. Mendez、P. R. Caron、C. Lin、M. A. Murcko、M. S. Collett和C. M. Rice，《病毒学杂志》71:5312 - 5322）。有趣的是，BDV预测的NS5A/5B切割位点的P1'由一个天冬酰胺残基代表。瞬时表达研究表明，这个不寻常的NS5A/5B加工位点被BDV的NS3丝氨酸蛋白酶有效切割。
