Studies on molecular determinants for virulence of lethal infection of infectious bursal disease virus

传染性法氏囊病病毒(IBDV)是雏鸡免疫抑制病的病原。根据对鸡的致死性，IBDV有两种类型，即强毒和经典型。然而，致死性差异的分子决定因素尚未确定。本研究以高致死率和低致死率的IBDV毒株为研究对象，对病毒结构蛋白VP2、VP3、VP4和非结构蛋白VP5的亚细胞定位进行了比较研究。此外，对每种病毒蛋白的细胞毒性进行了分析。对于VP2和VP5，使用细菌双杂交系统来确定与病毒蛋白相互作用的细胞分子。每种病毒蛋白的亚细胞定位比较研究表明，VP5在强毒型和经典型之间存在差异。此外，来自强毒株的VP5比来自经典型的VP5具有更高的细胞毒性。不幸的是，没有检测到与病毒蛋白相互作用的细胞分子。这些结果表明，VP5与IBDV强毒株的毒力有关。以往报道的氨基酸序列比对结果显示，强毒型和经典型的氨基酸序列存在4个氨基酸差异。VP5中仅有的4个氨基酸可能与强毒型IBDV的毒力有关。

Infectious bursal disease virus (IBDV) is the causative agent of immunosuppressive disease of young chicken. There are two types of IBDV based on the lethality for chicken, highly virulent and classical types. However, the molecular determinants for the difference of lethality have not been defined. In the present study, IBDV strains which show high mortality and low mortality designated as highly virulent type and classical type, respectively were used for comparative study of subcellular localization of viral structural proteins, VP2,VP3 and VP4, and nonstructureal protein VP5. In addition, cell toxicity of each viral protein was analyzed. For the VP2 and VP5, bacterial 2-hybrid system was used to determine the cellular molecules which interact with the viral proteins. Comparative study of subcellular localization of each viral protein showed that the VP5 showed differences between the highly virulent type and the classical type. Furthermore, VP5 derived from highly virulent strain showed higher cell toxixity than that of VP5 derived from classical type. Unfortunately, the cellular molecules which interact with the viral proteins were not detected. These results indicate that VP5 is responsible for the virulence of highly virulent IBDV. Previous report of the deduced amino acid sequence allignment showed 4 amino acid differences between the sequence of highly virulent type and classical type. The only 4 amino acids in VP5 may contribute to the virulence of highly virulent type of IBDV.