GENETIC STUDIES OF ROTAVIRUS PATHOGENESIS

轮状病毒发病机制的遗传学研究

• 批准号: 3790729
• 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/3790729
• 关键词: Rotavirus; diarrhea; disease /disorder model; newborn animals; rotavirus vaccines; swine; virulence; virus genetics; virus infection mechanism; virus protein

Continued efforts have been made to delineate the genetic mechanisms underlying virulence of rotavirus in the newborn gnotobiotic piglet model. A single gene substitution reassortant that had the 1st, 2nd, 5th, 6th, 7th, 8th, or 11th gene from human rotavirus DS-1 strain (which does not induce productive infection or diarrhea in gnotobiotic piglets) and the remaining ten genes from porcine rotavirus SB-1A strain (which consistently induces diarrhea in piglets) induced diarrhea in piglets that was associated with virus shedding. However, piglets challenged with a single gene substitution reassortant that had the VP3 gene, or VP4 gene, or VP7 gene, or NS-28 gene of DS-1 virus and the remaining ten genes from porcine SB-1A virus failed to develop illness or shed virus. Thus, we demonstrated that the 3rd, 4th, 9th (VP7), or 10th (NS28) gene each play an important role in virulence of rotavirus infection in piglets. Piglets challenged with a rotavirus reassortant that had the 3rd, 4th, 9th, and 10th genes of SB-1A virus and the remaining seven genes from DS-1 virus developed diarrhea and shed virus.

人们一直在努力阐明遗传机制， 轮状病毒在新生无菌仔猪模型中的潜在毒力。 一个单一的基因置换抗性，具有第1，第2，第5，第6， 来自人轮状病毒DS-1株的第7、第8或第11个基因（其不 在无菌仔猪中诱导生产性感染或腹泻）， 剩余的10个基因来自猪轮状病毒SB-1A株（其一致地 诱导仔猪腹泻）诱导仔猪腹泻， 与病毒脱落有关。 然而，用一种单一的 具有VP 3基因、或VP 4基因、或VP 7基因的基因置换抑制子 DS-1病毒的NS-28基因和其余10个来自猪的基因 SB-1A病毒没有发病或脱落病毒。 因此，我们证明了 第3、第4、第9（VP 7）或第10（NS 28）基因每个都发挥重要作用， 轮状病毒感染仔猪的毒力作用。 攻毒仔猪 与轮状病毒的第3，4，9和10个基因的重组体， SB-1A病毒和来自DS-1病毒的其余7个基因开发 腹泻和散播病毒。