高毒性人呼吸道合胞病毒鼠适应株的筛选

Screening of highly toxic human respiratory syncytial virus isolates in mice

目的以BALB/c小鼠作为动物模型筛选高毒性人呼吸道合胞病毒鼠适应株。方法以连续传代法经小鼠下呼吸道接种临床株人呼吸道合胞病毒hRSV-A-GZ08-0,确认8月龄BALB/c雄鼠作为人呼吸道合胞病毒动物模型较3周龄BALB/c小鼠和8月龄BALB/c雌鼠更佳后,以8月龄BALB/c雄鼠为动物模型,将hRSV-A-GZ08-0连续传代50代,分离获得1株鼠适应株hRSV-A-GZ08-P50-4,该株病毒与临床株hRSV-A-GZ08-0分别接种8月龄BALB/c雄鼠后第3d以TCID50方法测定鼠肺灌洗液中的病毒滴度,并作鼠肺病理切片比较两株病毒感染的不同。结果8月龄BALB/c雄鼠作为人呼吸道合胞病毒动物模型较3周龄BALB/c小鼠和8月龄BALB/c雌鼠更佳。与临床株hRSV-AGZ08-0比较,hRSV-A-GZ08-P50-4为高毒性hRSV鼠适应株。结论 8月龄BALB/c小鼠,特别是8月龄BALB/c雄鼠,可作为动物模型筛选高滴度hRSV鼠适应株。筛选到的高毒性hRSV鼠适应株hRSV-A-GZ08-P50-4致病力较强。

Objective The aim of this study was to screen highly toxic human respiratory syncytial virus isolates in BALB/c mice. Methods A clinical isolate of human respiratory syncytial virus （hRSV-A-GZ08-0） was serially passaged and then mice were intratracheally inoculated with the virus. Eight-month old male BALB/c mice served as a model of hu- man respiratory syncytial virus infection and were compared to 3-week-old male BALB/c mice and 8-month old female BALB/c mice. hRSV-A-GZ08 0 was serially passaged 50 times to yield a murine isolate （hRSV-A-GZ08-P50-4） that was then purified. The infectivity of hRSV-A GZ08-PS0-4 and hRSV-A-GZ08-0 was compared in 8-month-old male BALB/c mice via a TCIDS0 assay and lung section H/E staining. Results 1. Compared to 3-week-old BALB/c mice and 8- month-old female BALB/c mice, 8-month old male BALB/c mice provided a better animal model with which to yield the highly toxic human respiratory syncytial virus isolate. 2. Compared to hRSV-A-GZ08-0, hRSV-A GZ08-P50-4 was a more toxic strain of human respiratory syncytial virus. Conclusion Eight-month-old male BALB/c mice provided a bet ter animal model with which to screen highly toxic human respiratory syncytial virus isolates. Highly toxic isolates of hu- man respiratory syncytial virus were successfully screened in BALB/c mice, and that process yielded the strain hRSV-A- GZ08-P50-4.