Tang Fangqiang, Pan Zishu, Zhang Chuyu
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Virus Res. 2008 Feb;131(2):132-5. doi: 10.1016/j.virusres.2007.08.015. Epub 2007 Oct 24.
Classical swine fever virus, one member of the family Flaviviridae, is the pathogen of CSF, an economically important and highly contagious disease of pigs. Knowledge of virus genes under positive selection pressure can help identify molecular determinants of virulence or pathogenesis without prior knowledge of the mechanisms governing virulence and pathogenesis and clarify the driving force of classical swine fever virus evolution. The positive selection pressure acting on envelope protein genes E(rns), E1 and E2 of classical swine fever virus were assessed and a site-by-site analysis of the d(N)/d(S) ratio was performed, to identify specific codons undergoing diversifying positive selection. Whilst no significant evidence for positive selection was observed in E1, four positively selected sites (208 in E(rns) and 72, 75, and 200 in E2) were identified. The positively selected site (208) of E(rns) corresponds to one of the amino acid substitutions (Ser to Arg) found in an HS-binding CSFV variant. The mutant at the positively selected site (75) is located within an O-glycosylation motif and altered the predicted glycosylation pattern. In addition, Thr at the positively selective site 200 are directly involved with mAb WH308 with which CS vaccine strain does not react, unlike most of the virulent CSFV strains.
古典猪瘟病毒是黄病毒科的成员之一,是猪瘟的病原体,猪瘟是一种对经济有重要影响且传染性很强的猪病。了解处于正选择压力下的病毒基因有助于在不预先了解毒力和发病机制的情况下识别毒力或发病机制的分子决定因素,并阐明古典猪瘟病毒进化的驱动力。评估了作用于古典猪瘟病毒包膜蛋白基因E(rns)、E1和E2的正选择压力,并对d(N)/d(S)比率进行了逐个位点分析,以识别经历多样化正选择的特定密码子。虽然在E1中未观察到正选择的显著证据,但鉴定出了四个正选择位点(E(rns)中的208位以及E2中的72、75和200位)。E(rns)的正选择位点(208)对应于在一种与HS结合的古典猪瘟病毒变体中发现的氨基酸替代之一(丝氨酸到精氨酸)。正选择位点(75)处的突变位于一个O-糖基化基序内,并改变了预测的糖基化模式。此外,与大多数强毒古典猪瘟病毒株不同,正选择位点200处的苏氨酸直接与单克隆抗体WH308相互作用,而古典猪瘟疫苗株不与该单克隆抗体发生反应。