小鼠人偏肺病毒感染模型的建立

Establishment of mouse model for human metapneumovirus infection

目的建立人偏肺病毒（hMPV）感染小鼠模型，了解病毒肺内复制规律及所致病理改变，为hMPV感染免疫病理机制研究及新型防治手段开发奠定基础。方法BALB／c小鼠经滴鼻感染荧光标记的重组hMPV，于感染后1、3、5、7、9、16d处死小鼠并无菌获取肺组织用于病毒分离和病理检查，改良噬斑形成法检测hMPV滴度，RT—PCR法检测hMPVmRNA表达。结果小鼠滴鼻感染hMPV后肺组织分离到病毒；肺组织病毒滴度在感染后5d达到高峰（5．16±1．09）×10^5PFU／g，感染后第9天仍能检测到病毒（2．79±1．22）×10^2PFU／g；感染后16d肺组织仍可检测到hMPV mRNA；病理改变在感染后3～7d最明显，为典型的间质性肺炎改变。结论hMPV感染BALB／c小鼠模型建立成功，可用于hMPV感染的免疫病理机制研究。

Objective To establish a mouse model for human metapneumovirus （hMPV） infection, and to explore the course of viral replication and pathology and lay ground for vaccine development. Methods BALB/c mice were infected intranasally with hMPV, and sacrificed on day 1,3, 5,7, 9 and 16 post inoculation. Lungs were used for viral isolation, viral titration by an improved plaque assays, pulmonary histopathology and detection of hMPV mRNA expression by RT-PCR. Results Live viruses were successfully isolated from the lungs of infected mice, hMPV replicate well in the lungs and viral titers peaked on the 5th day post inoculation （5.16 ± 1.09） ×10^5 PFU/g, remaining to be detectable on the 9th day post inoculation （2.79 ± 1.22） ×10^2 PFU/g. Genomic RNA of hMPV was able to be detected on the 16th day post inoculation by RT-PCR targeting F gene. Histopathology of lungs was characterized by interstitial pneumonia in particular during 3-7 days post inoculation. Conclusion hMPV infected BALB/c mice model was successfully established, hMPV infected mice showed similar patterns of viral replication and pulmonary histopathology as in infected humans.