Effects of MyD88^-/- mice with rabies virus intracerebral infection on lung pathological changes

【Objective】 To clarify the effects of intracerebral infection withrabies virus(RABV) of myD88 gene elimination(MyD88^-/-) miceon pulmonary pathology,and to explore the delay effect of myD88 gene loss on the pathogenesis of rabies,so as to lay the foundation for further elucidation of the pathogenesis of RABV.【Method】 Using MyD88^-/- and wild-type(MyD88^+/+) mice intracerebrally-infected with the weakened strain rRC-HL of RABV and the standard strain CVS-24 respectively,the attack dose was 1000 FFU/mouse for each group. Also,DMEM was vaccinated with the same method and dose as comparisons. Through observing symptoms and changes in body mass of mice after the intracerebral poisoning,collecting brain tissue and lungs on the 4^th and 7^th days after intracranial poisoning,and detecting the expression of viral genes and cytokines in each group's brain tissue and lungs through real-time fluorescence quantitative PCR, lung tissue sections were prepared to observe the pathological changes.【Result】 MyD88^+/+ and MyD88^-/- mice showed mild symptoms after brain infection with the weak strain rRC-HL,while the standard strain CVS-24 was fatal to both groups of mice. Compared with MyD88^+/+ mice, MyD88^-/- mice had delayed onset time and death time by 1 to 2 d. The group of mice which was intracerebrally infected with both species of the weak strain rRC-HL recovered from the 10^th day and the symptoms gradually disappeared,but MyD88^-/- mice recovered faster than MyD88^+/+ mice. After intracerebral infection with RABV,the expression of relevant cytokines(IFN-α,IFN-γ,IL-1β,MCP-1,and TNF-α) in the brain tissue of mice was changed,while only a small portion of the differential multiplicity of the expression in the lungs was more than 2.00 times,and the changes showed irregularities with the time of the attack. In addition,the observation of lung tissue sections from near-death mice revealed that the MyD88^+/+ mice had deep nuclear staining, slight thickening of the alveolar wall,slight inflammatory changes,and macrophages. At the same time,MyD88^-/- mice lung tissue section cells were lightly pigmented,alveolar wall thickening was not obvious,inflammatory changes were mild,and there were a small number of macrophages infiltration.【Conclusion】 The 7^th day after intracerebral poisoning is the period when RABV has the strongest ability to replicate in mouse brain tissue,and the expression difference in brain tissue-related cytokines changes greatly with the course of the disease. Also,lung tissue sections did not reveal typical characteristic pathological changes,but the effect of RABV infection on lung pathology in MyD88^-/- mice is less than that of MyD88^+/+ mice. In conclusion,the loss of the MyD88 gene helps mice fight RABV infection,inhibits inflammation,and delays the pathogenesis of the body.