H5N1亚型禽流感病毒低剂量感染小鼠发病模型的建立

Pathogenicity of a low-dosage inoculation of H5N1 avian influenza virus in mice

为模拟哺乳动物感染H5亚型高致病性禽流感病毒(HPAIV)的发病进程,本研究采用对哺乳动物高度致病的 H5N1 亚型 HPAIV 株 A/bar-headed goose/Qinghai/3/05(BHG/3/05),以低剂量鼻腔接种小鼠,观察发病、存活、病毒复制及组织病理损伤情况。结果显示,100.4EID50即能够100%感染小鼠,但发病表现缓慢,死亡延迟至8d以后,存活达60%;体内病毒复制可持续10d以上,感染后前3d病毒的增殖限于呼吸道,随后扩散至脑、脾、肾等其他器官;组织病理学观察肺脏早期表现出渗出性炎症,第10d发展为典型的间质性肺炎。本研究结果为探讨人禽流感的病理发生机制提供了具有价值的模型。

To imitate the natural infection of H5N1 subtype avian influenza virus （AIV） in animals, BALB/c mice were inoculated with a low-dosage （10^0.4 EID50） of H5N1 A1V A/bar-headed goose/3/05 （BHG/3/05） strain and were observed for weight gain and mortality. Different organs of the mice were also collected at different time points after infection for virus titration and pathologic examination. The results indicated that all of the inoculated mice were successfully infected by the virus, and 60% of mice survived during the 2 weeks observation period. Virus could be detected from organs of mice at 3, 5, 7, and 10 days, but not at 14 days post infection （p.i.）. The virus was only detected in the lung of mice on day 3 p.i., then gradually spread to spleen, kidney and brain. Histopathologic examination revealed the pneumonia with significant infiltration of inflammatory cells in the lung section at day 3 p.i., and interstitial pneumonia at day 10 p.i.. These results are useful for a better understanding of the pathogenesis of H5N1 influenza virus infection in nature.