不同免疫状态的小鼠对禽流感病毒H5N1感染的敏感性及其机制探讨

Susceptibility of mice strains in different immune status to avian influenza virus H5N1 infection and the possible mechanism

目的比较不同免疫状态的小鼠对禽流感病毒的易感性,并探讨可能的原因。方法四种免疫状态的小鼠,无菌BALB/c小鼠,SPF级BALB/c小鼠,SCID小鼠和nude小鼠,以10 TCID50的禽流感病毒50μL感染小鼠,观察小鼠的体重变化,存活率,各组织脏器的病毒分布,肺组织的细胞因子变化和肺组织病理病变。结果四种小鼠均能感染禽流感病毒,其中,无菌小鼠对禽流感病毒H5N1的易感性最低,存活率最高。并且病毒在无菌鼠体内病毒的复制水平最低,细胞因子TNF-α,IL-12,MIP2,GATA3,IFN-a/β在感染后表达水平最低,其中第7天最低。结论无菌小鼠能感染禽流感病毒,但是相比较SPF级BALB/c小鼠,SCID小鼠和nude小鼠,其易感性最低,可能与病毒在组织内的低复制和细胞因子的低表达均有关。

Objective To compare the susceptibility of different mice strains in different immune status to H5N1 virus,and investigate the possible mechanism.Methods Germ free BALB/c mice,SPF BALB/c mice,SCID mice and nude mice were challenged with 50 μL 10 TCID50 H5N1 virus,then the body weight and survival were observed daily.In addition,the virus distribution in tissues,the cytokines in the lung,and pathological changes of the lung were also monitored.Results The four different strains of mice could be infected by H5N1 virus successfully.The germ free mice were the lowest susceptible animals,with lowest virus replication in GF mice tissues and lowest cytokine level,including TNF-α,IL-12,MIP2,GATA3,IFN-α/β/γ,especially at the 7th day.Conclusions Germ free mouse is the lowest susceptible animal to H5N1 among the four mouse strains： germ-free BALB/c,SPF BALB/c,nude and SCID mice,due to low level of virus replication and low cytokine expression.