H7N9禽流感病毒小鼠感染动物模型的建立

目的建立H7N9禽流感病毒小鼠感染模型。方法 1×108,1×107或1×106TCID50H7N9禽流感病毒原液(A/Anhui/1/2013)滴鼻感染BALB/c小鼠。主要观测指标:临床症状、死亡率、病理变化、病毒载量和血清抗体检测。结果被感染的小鼠表现为竖毛、弓背、体重下降;病理表现为间质性肺炎,感染后第2天开始在呼吸道脱落细胞中检测到病毒;免疫组化或病毒分离方法在肺、肾、脑、肠、脾等组织检测到病毒;感染后14 d在小鼠血清中血凝抑制试验特异性抗体效价达到160;淋巴细胞减少,中性粒细胞增多。结论 H7N9感染BALB/c小鼠模型与人类禽流感感染疾病的基本特征相似,为研究该病的发病机制及药物疫苗的研发提供了工作基础。

Establishment of a mouse model of H7N9 avian influenza A virus infection

Objective The aim of this study was to establish a mouse model of H7N9 avian influenza A virus infection. Methods Seventy SPF healthy female BALB/c mice were used in this study. A/Anhui/1/2013 （H7N9） avian influenza virus was administered by intranasal instillation to BALB/c mice, inoculated in a dose of 50 μL 1×108, 1×107 or 1×106 TCID50, respectively, 10 mice in each group. Other 30 mice were used for virus titration and pathological examination. Ten mice were given saline as control group. The changes of body weight, clinical signs and death of the mice were observed every 24 h from 1 to 14 d. Blood and several organ samples were taken for pathological examination, and avian influenza A （H7N9） virus was detected with virus titration and immunohistochemistery （IHC）. Results The mice developed typical clinical signs including body weight loss, ruffled fur and humped back. The peak of virus shedding from respiratory tract was observed on 2 days post inoculation （d.p.i.）, and histopathological examination observed interstitial pneumonia. The virus was also detected in the brain, liver, spleen, kidney and intestine from inoculated mice. The inoculation of H7N9 virus elicited seroconversion titers up to 160. There was reduction of lymphocytes and increase of neutrophils in the blood. Conclusions The mouse model of H7N9 avian influenza virus infection established in this study show similar signs of human avian influenza. Therefore, it provides a useful working basis for research of the pathogenesis, drug development, and vaccine evaluation of this disease.