甲型H1N1流感病毒对未孕雌鼠及孕鼠的致病性研究

Pathogenicity of the 2009 A(H1N1) influenza virus in mice and pregnant mice

目的应用A/Changchun/01/2009(H1N1)(简称XD09)分别感染未孕昆明雌鼠和孕鼠,研究甲型H1N1流感病毒对怀孕哺乳动物的致病性差异。方法 XD09鼻内接种8周龄雌性未孕雌鼠和孕鼠,于感染后第2 d各处死3只,分别检测病毒在鼠脑、鼻甲骨、肺、肝、脾、肾、胎盘(孕鼠)中的分布,同时计算病毒的MLD50,并观察感染鼠临床症状。结果未孕昆明雌鼠感染XD株病毒后第2 d出现被毛粗乱,呼吸窘迫,体重下降;病毒主要分布在肺脏和鼻甲骨,滴度分别为(5.83±0.29)log10eID50/ml和(3.42±0.38)log10eID50/ml,脾组织也检测到病毒的复制;该病毒对未孕雌鼠的MLD50为6.25 log10eID50。昆明孕鼠感染后第3 d开始出现被毛粗乱、活动减少等轻微临床症状,但未见明显的呼吸窘迫,其中1只孕鼠攻毒后流产并产下木乃伊胎儿;病毒主要分布在肺脏和鼻甲骨等呼吸道组织,滴度分别为(5.07±0.55)log10eID50/ml和(4.08±0.29)log10eID50/ml,脑组织也检测到病毒的复制;该病毒对孕鼠的MLD50>6.5 log10eID50。结论甲型H1N1流感病毒不需要传代适应就能够直接感染未孕雌鼠,而季节性流感病毒通常需要在未孕雌鼠体内连续传代适应后才可在其肺部有效地复制,因此该病毒对未孕雌鼠的致病性要强于季节性流感病毒。研究还发现病毒在未孕雌鼠和孕鼠间表现出不同的组织嗜性,为近一步研究H1N1流感病毒感染孕妇病死率偏高现象建立了动物实验模型。

Objective To investigate the pathogenic differences in pregnant mammals infected with 2009 A（H1N1） influenza virus.Kunming mice and pregnant Kunming mice were inoculated with A/Changchun/XD/09（H1N1）（XD09） virus.Methods Eight-week-old Kunming mice and pregnant mice were inoculated intranasally with XD09,respectively,and three mice and 3 pregnant mice were sacrificed on day 2 postinoculation.The viral distribution in the organs of mice and pregnant mice was detected,and the MLD50 was determined for XD09 that caused a lethal infection in mice.The clinical symptoms postinoculation were also observed.Results The virus-associated illnesses of Kunming mice included roughened hair coats,respiratory distress,and weight loss.The virus was titrated in lung tissue and turbinate bones.The titer in the lung was（5.83±0.29） log10eID50/ml,and the titer in turbinate bones was（3.42±0.38） log10eID50/ml.In addition,virus was also detected in the spleen.The MLD50 of virus in Kunming mice was 6.25 log10eID50.Virus-associated illnesses of pregnant Kunming mice included roughened hair coats and inactivity,and no marked respiratory distress was noted.A pregnant mouse inoculated with viruses miscarried.The virus was titrated in lung tissue and turbinate bones.The titer in the lung was（5.07±0.55） log10eID50/ml,and the titer in turbinate bones was（4.08±0.29） log10eID50/ml.In addition,virus was detected in the brain.The MLD50 of virus in pregnant Kunming mice was 6.5 log10eID50.Conclusion XD09 efficiently replicated in mice without successive passaging,indicating that the 2009 A（H1N1） influenza virus has a higher virulence for mice.The tissue tropism of the 2009 A（H1N1） influenza virus differed in mice and pregnant mice,so pregnant mice may serve as a model to study pathogenicity in pregnant women infected with this virus.