T Cells Facilitate Recovery from Venezuelan Equine Encephalitis Virus-Induced Encephalomyelitis in the Absence of Antibody
T Cells Facilitate Recovery from Venezuelan Equine Encephalitis Virus-Induced Encephalomyelitis in the Absence of Antibody
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DOI：
10.1128/jvi.02545-09
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Johnston, Robert E.
中科院分区：
文献类型：
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作者：
Brooke, Christopher B.;Deming, Damon J.;Johnston, Robert E.
委内瑞拉马脑炎病毒(VEEV)是一种由蚊子传播的甲型病毒属核糖核酸病毒，通过在人类和马群中零星爆发，导致中南美洲的重大疾病负担。对于人类来说，2%至4%的病例与脑炎有关，总体病例死亡率约为1%。在小鼠中，病毒在中枢神经系统(CNS)的神经元内复制会导致瘫痪，永远是致命的脑脊髓炎。然而，感染了该病毒某些减毒突变的小鼠能够控制中枢神经系统内的感染并康复。为了更好地确定T细胞反应在这一过程中可能扮演的角色，我们用一种VEEV突变体感染B细胞缺陷的Mu MT小鼠，该突变体可以在免疫能力强的小鼠中诱导轻微的亚致死性疾病。感染的MU MT小鼠迅速出现严重瘫痪脑脊髓炎的临床症状，但最终能够控制感染并从临床疾病中完全康复。在这个系统中的恢复依赖于T细胞，并与中枢神经系统内病毒滴度的显著降低有关，随后病毒在大脑中持续存在。进一步比较T细胞亚群在该系统中的相对作用，发现CD4(+)T细胞比CD8(+/-)T细胞更能产生干扰素(干扰素-γ)，并且在控制中枢神经系统内的VEEV方面更有效。总体而言，这些结果表明T细胞，特别是CD4(+)T细胞，可以成功地控制中枢神经系统内的VEEV感染，并促进从严重的病毒性脑脊髓炎中恢复。
Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus of the genus Alphavirus that is responsible for a significant disease burden in Central and South America through sporadic outbreaks into human and equid populations. For humans, 2 to 4% of cases are associated with encephalitis, and there is an overall case mortality rate of approximately 1%. In mice, replication of the virus within neurons of the central nervous system (CNS) leads to paralyzing, invariably lethal encephalomyelitis. However, mice infected with certain attenuated mutants of the virus are able to control the infection within the CNS and recover. To better define what role T cell responses might be playing in this process, we infected B cell-deficient mu MT mice with a VEEV mutant that induces mild, sublethal illness in immune competent mice. Infected mu MT mice rapidly developed the clinical signs of severe paralyzing encephalomyelitis but were eventually able to control the infection and recover fully from clinical illness. Recovery in this system was T cell dependent and associated with a dramatic reduction in viral titers within the CNS, followed by viral persistence in the brain. Further comparison of the relative roles of T cell subpopulations within this system revealed that CD4(+) T cells were better producers of gamma interferon (IFN-gamma) than CD8(+/-) T cells and were more effective at controlling VEEV within the CNS. Overall, these results suggest that T cells, especially CD4(+) T cells, can successfully control VEEV infection within the CNS and facilitate recovery from a severe viral encephalomyelitis.