H1N1流感病毒树鼩模型生物学特性的研究

Biological characteristics of a tree shrew model infected with H1N1 influenza virus

目的建立H1N1流感病毒感染树鼩模型,探讨流感病毒动力学变化和在呼吸系统组织中的分布特征。方法选择3~3.5周岁成年树鼩(Tupaia Belangeri Chinensis)24只,雌雄各半,随机分为空白组(B组)和模型组(M组)各12只,使用H1N1流感病毒每只600μL(1×10^(6.8)TCID50/0.1 mL)经鼻腔感染M组树鼩,在-3~10 d期间每天早晨测量肛温,同时采集咽拭子、鼻拭子和血液样本测定病毒载量。并测定2、4、7 d血液中抗流感的中和抗体。2、3、5、10 d随机处死3只树鼩,采集鼻甲、气管、咽部和肺组织进行病毒载量检测,取3、5、10 d组织进行病理学检测。结果M组的树鼩表现为被毛蓬乱、食欲不振、运动迟缓、体温升高和鼻咽分泌物增加等临床症状;感染后1 d开始可以在呼吸道中检测到病毒载量,3 d血液中出现病毒载量;病理结果显示鼻甲、咽、气管和肺组织中均有一定程度的病理改变。结论树鼩感染流感病毒后出现的临床症状与人类极为相似,所建立的流感树鼩模型对研究流感的发病机制与抗流感药物评价提供了有重要价值的工具。

Objective To establish a tree shrew model of H1 N1 influenza virus infection and to explore the dynamics of the influenza virus and its distribution in respiratory tissues.Methods Twenty-four 3 to 3.5-years-old adult tree shrews(Tupaia Belangeri Chinensis),with equal numbers of males and females,were randomly divided into a blank group(group B)and a model group(group M)of 12 tree shrews each.H1 N1 influenza virus 600μL/bird(1×10^(6.8)TCID50/0.1 mL)were inoculated into M group tree shrews through the nasal cavity;the rectal temperature was measured every morning from rom 3 d before until 10 d after inoculation,and throat swabs,nasal swabs,and blood samples were collected to determine the viral load.Blood levels of neutralizing antibodies against influenza were determined on days 2,4,and 7.Three tree shrews were randomly sacrificed on days 2,3,5,and 10,turbinate,trachea,pharynx,and lung tissues were collected for viral load detection,3,5,and 10 days of tissue were taken for histopathology.Results Tree shrews in group M showed clinical symptoms such as a disheveled coat,loss of appetite,slow movement,increased body temperature,and increased nasopharyngeal secretion,and their blood viral load appeared.There were some pathological changes to the turbinate,pharynx,trachea,and lung tissue of group M.Conclusions The clinical symptoms of tree shrews infected with influenza virus were very similar to those of humans.The established influenza virus tree shrew model provides a valuable tool for studying the pathogenesis of influenza and evaluating anti-influenza drugs.