GENETIC STUDIES OF ROTAVIRUS PATHOGENESIS

轮状病毒发病机制的遗传学研究

• 批准号: 5200443
• 负责人: Y HOSHINO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200443
• 关键词: Rotavirus; attenuated microorganism; diarrhea; genetic strain; pathologic process; recombinant virus; swine; virulence; virus genetics

Previously, in studies involving a semi-homologous system of gnotobiotic newborn pigs and a virulent porcine rotavirus strain (SB-1A) and an avirulent human rotavirus strain (DS-1) and their reassortants, we demonstrated that: (i) the third (VP3), fourth (VP4), ninth (VP7), or tenth (NS28) porcine rotavirus gene each play an important independent role in the virulence of rotavirus infection in piglets; and (ii) all four of the porcine rotavirus virulence-associated genes are required for the induction of diarrhea and the shedding of a virus by piglets. These observations suggested a potential new strategy for attenuation of wild- type human rotaviruses of major epidemiologic importance and its application to the development of a safe and effective vaccine. Based on this strategy efforts were made to generate four human x bovine rotavirus reassortants, each of which has: (i) the VP4-encoding gene from human rotavirus Wa (VP4:1A); (ii) the VP7-encoding gene from human rotavirus D (VP7:1), DS-1 (VP7:2), P (VP7:3), or ST3 (VP7:4); and (iii) the remaining nine genes including the VP3-encoding gene and NS28- encoding gene from bovine rotavirus UK. In addition, we successfully generated two human x bovine rotavirus reassortants, each of which had the VP4-encoding gene from human rotavirus Wa (VP4:1A) or DS-1 (VP4:1B) and the remaining ten genes from bovine rotavirus UK. More recently, we have generated two additional human x rhesus rotavirus reassortants, each of which has the VP4-encoding gene from human rotavirus Wa (VP4:1A) or DS-1 (VP4:1B), the VP7-encoding gene from human rotavirus DS-1 (VP7:2) and the remaining nine genes from rhesus rotavirus MMU18006. Such strains may be important in the development of an optimally effective rotavirus vaccine.

此前，在涉及灵知生菌半同源系统的研究中 新生猪和一株强毒猪轮状病毒(SB-1A)和一只 人轮状病毒弱毒株(DS-1)及其重组体 证明：(1)第三(VP3)、第四(VP4)、第九(VP7)或 猪轮状病毒第十代(NS28)基因各自独立发挥重要作用 在轮状病毒感染仔猪的毒力中所起的作用；及 猪轮状病毒毒力相关基因中的四个是 仔猪引起的腹泻和病毒的排出。这些 观察表明了一种潜在的新策略来减弱野生- 具有重要流行病学意义的人轮状病毒及其临床应用 应用于开发安全有效的疫苗。 基于这一策略，我们努力培育出了四个人×牛 轮状病毒重组体，每个重组体都有：(I)VP4编码基因 来自人类轮状病毒Wa(VP4：1A)；(Ii)来自人类的VP7编码基因 轮状病毒D(VP7：1)、DS-1(VP7：2)、P(VP7：3)或ST3(VP7：4)；及(Iii) 其余9个基因包括VP3编码基因和NS28- 编码牛轮状病毒UK基因。此外，我们还成功地 产生了两个人x牛轮状病毒重组体，每个重组体都有 人轮状病毒Wa(VP4：1A)或DS-1(VP4：1B)的VP4编码基因 剩下的10个基因来自牛轮状病毒英国。最近，我们 产生了另外两个人x恒河猴轮状病毒重组体，每个重组体 其中具有来自人类轮状病毒WA(VP4：1A)的VP4编码基因或 人轮状病毒DS-1(VP7：2)VP7编码基因DS-1(VP4：1B) 剩下的9个基因来自恒河猴轮状病毒MMU18006。是这样的 菌株可能在最佳效果的发展中很重要 轮状病毒疫苗。