两株H6亚型禽流感病毒变异株的生物学特性分析

Biological characteristics of two variants of A/H6N1 avian influenza virus

目的研究两株H6亚型禽流感病毒变异株对小鼠的致病性,并建立H6亚型禽流感病毒变异株感染BALB/c小鼠动物模型,为病毒的致病机理、抗病毒药物研究及其疫苗评价提供实验平台。方法 106EID50/50μl～101EID50/50μl病毒经鼻内接种小鼠,在攻毒后第3、5d分别剖杀小鼠,无菌取脏器,分析病毒在不同时间不同脏器的复制水平,观察小鼠临床症状、脏器的病毒滴定水平,小鼠体重变化情况及生存率,评估变异株病毒对小鼠的易感性和致病性,同时对肺脏进行病理学检查和免疫组化分析。结果与亲代毒株相比较,小鼠感染两变异株后体重明显下降直至死亡,组织滴定显示病毒不仅能在肺和鼻甲骨复制,还能入侵小鼠的脑组织。免疫组化显示感染后小鼠肺脏有变异株病毒分布。结论经小鼠肺脏传代获得的2株H6亚型禽流感病毒变异株对小鼠具有易感性和致病性。建立的小鼠动物模型可用于H6亚型禽流感病毒致病机制、感染特点、病毒疫苗的研制及药物效果的评价。

Objective This study evaluated the pathogenicity of two variants of A/H6N1 AIV and it successfully constructed a model of infection in order to provide information on and facilitate the evaluation of an A/H6N1 AIV vaccine. Methods Mice were inoculated intranasally with 106 EID50/50 μl-101 EID50/50 μl of the variants. Mice were sacrificed on days 3 and 5 post-infection to analyze levels of viral replication in different organs at different times. Virological data were collected by observing clinical symptoms, determining viral titers, and measuring changes in body weight and survival rates in order to evaluate the susceptibility to and pathogenicity of the A/H6N1 AIV in mice. Histological data were collected by pathological examination and immunohistochemistry. Results Compared to the A/H6N1 AIV, mice infected with the variants had a marked decrease in body weight that even resulted in death. Titers revealed that the virus replicated in the lungs and nasal turbinates but also invaded the brain. Immunohistochemistry results revealed viral antigens within the lungs. Conclusion Variants of A/H6N1 AIV were pathogenic to mice, which were susceptible to the virus. A mouse model of infection can be used to evaluate the mechanisms of the H6N1 influenza virus＇ pathogenicity and the characteristics of its infection. The model can also be used to prepare vaccines and evaluate the efficacy of drugs.