Sequence variability and evolution of the terminal overlapping VP5 gene of the infectious bursal disease virus
Sequence variability and evolution of the terminal overlapping VP5 gene of the infectious bursal disease virus
复制标题
DOI：
10.1007/s11262-010-0485-4
复制
发表时间：
2010-08-01
期刊：
影响因子：
1.6
通讯作者：
Perez, Ruben
中科院分区：
文献类型：
--
作者：
Hernandez, Martin;Villegas, Pedro;Perez, Ruben
传染性法氏囊病病毒（IBDV;双核糖核酸病毒科）构成了全世界家禽业的主要威胁之一。该病毒的分子流行病学的大部分进展是通过对衣壳蛋白VP 2编码区的研究取得的。关于其他IBDV基因组区域的遗传变异的分子进化和流行病学意义的研究很少。本文对编码非结构蛋白VP 5的基因进行了分析。虽然该蛋白不是病毒复制所必需的，但最近的证据表明它可能与病毒的毒力表型和适应能力有关。VP 5基因也具有进化上的意义，因为它具有与pVP 2-VP 4-VP 3多蛋白编码区末端重叠的开放阅读框。在本研究的第一部分中，对南美株的完整VP 5基因进行了表征。结果显示，乌拉圭超强力IBDV毒株（vvIBDV）的VP 5基因缺乏迄今为止已描述的vvIBDV毒株的替代性AUG起始密码子特征。相反，如在经典毒株和变异毒株中所发生的，该VP 5基因具有位于下游四个密码子的AUG起始位点，因此，它编码145个氨基酸长的蛋白质，而不是其它vvIBDV的推定的149个氨基酸长的蛋白质。尽管如此，这些病毒保留了超强毒株的VP 5和VP 2氨基酸特征，并与参考vvIBDV序列聚类。这一发现可能代表了VP 5基因可以通过改变翻译起始位点而进化的证据。在本研究的第二部分中，包括本研究中报道的序列以及GenBank中可获得的大多数VP 5序列的进化分析表明，存在一个复杂的选择压力系统控制VP 5基因的进化。使用dN/dS指数，我们发现在VP 2的5'末端重叠区域上施加了强烈的纯化选择，这将限制VP 5的进化。这些结果加强了VP 5基因起源于IBDV进化后期的遗传重叠机制的假设。本研究中描述的结果提供了有关IBDV基因组动态的新信息，并揭示了该病毒进化中的一些机制。由于VP 5似乎与病毒的致病性有关，因此这种进化信息可能有助于突出该蛋白的遗传变异对IBDV流行病学的影响。
The infectious bursal disease virus (IBDV; Birnaviridae family) constitutes one of the main threats to the poultry industry worldwide. Most of the progress in the molecular epidemiology of this virus has been achieved through the study of the coding region of the capsid protein VP2. Little research has been done regarding the molecular evolution and the epidemiological implications of genetic variability of other IBDV genome regions. In this article, the gene that codes the non-structural protein VP5 was analyzed. Although this protein is not essential for the virus replication, recent evidence indicates that it could be related to the virulent phenotype and the adaptive capacity of the virus. The VP5 gene is also of evolutionary interest because it has an open reading frame that terminally overlaps with the pVP2-VP4-VP3 polyprotein coding region. In the first part of this study, the full VP5 gene of a South American strain was characterized. The results revealed that the VP5 gene of Uruguayan hypervirulent IBDV strains (vvIBDV) lacks the alternative AUG start codon characteristic of the vvIBDV strains that have been described to date. Instead, as occurs in classic and variant strains, this VP5 gene has an AUG start site located four codons downstream and, consequently, it codes for a 145 amino acid long protein rather than the putative 149 amino acid long protein of other vvIBDV. In spite of this, these viruses conserved the VP5 and VP2 amino acid signature of the hypervirulent strains and clustered with reference vvIBDV sequences. This finding may represent evidence that the VP5 gene could be evolving by changing the translation initiation site. In the second part of this study, an evolutionary analysis including the sequences reported in this study together with most of VP5 sequences available in the GenBank, showed the existence of a complex system of selective pressures controlling the evolution of the VP5 gene. Using the dN/dS index, we found a strong purifying selection exerted on the 5' terminal overlapping region of VP2 that would be constraining the evolution of VP5. These results reinforce the hypothesis that the VP5 gene was originated late in the IBDV evolution by a mechanism of genetic overprinting. The results described in this study provided new information about the dynamics of the IBDV genome and revealed some of the mechanisms at play in the evolution of this virus. Since VP5 seems to be related to viral pathogenicity, this evolutionary information might be useful to highlight the impact of the genetic variation of this protein on the epidemiology of IBDV.