Mouse hepatitis virus is cleared from the central nervous systems of mice lacking perforin-mediated cytolysis
Mouse hepatitis virus is cleared from the central nervous systems of mice lacking perforin-mediated cytolysis
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DOI：
10.1128/jvi.71.1.383-391.1997
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发表时间：
1997-01-01
影响因子：
5.4
通讯作者：
Hinton, DR
中科院分区：
文献类型：
--
作者：
Lin, MT;Stohlman, SA;Hinton, DR
用两株JHM病毒（JHMV）感染穿孔素缺陷型[穿孔素（-/-）]小鼠，以分析穿孔素介导的细胞毒性在急性致死性和亚急性中枢神经系统（CNS）感染中的作用。在急性和亚急性感染期间，穿孔素（-/-）小鼠的总体死亡率与对照组没有差异。穿孔蛋白（-/-）小鼠比对照组存活更长时间，与发病率降低一致。与对照组一样，两种病毒株均从穿孔素（-/-）小鼠中清除;然而，穿孔素（-/-）小鼠的清除速率延迟，表明穿孔素介导的细胞溶解参与了病毒清除。缺乏穿孔素介导的细胞溶解并不能预防脑脊髓炎或广泛的脱髓鞘。在穿孔素（-/-）和对照组的CNS中检测到经历凋亡的细胞，表明穿孔素对于程序性细胞死亡不是必需的。直到感染后第9天，大部分病毒被清除，才在两组小鼠中检测到中和抗体。这些数据进一步证实了细胞介导的细胞毒性的重要性，并表明免疫应答的其他组分有助于从CNS中清除JHMV。
Perforin-deficient [perforin (-/-)] mice were infected with two strains of JHM virus (JHMV) to analyze the role of perforin-mediated cytotoxicity in acute lethal and subacute central nervous system (CNS) infections. During both acute and subacute infections, the overall mortality of the perforin (-/-) mice was not different from that of the controls. Perforin (-/-) mice survived longer than the controls, consistent with reduced morbidity. Both strains of virus were cleared from the perforin (-/-) mice as in the controls; however, the rate of clearance was delayed in the perforin (-/-) mice, indicating that perforin-mediated cytolysis is involved in viral clearance. The absence of perforin-mediated cytolysis did not prevent encephalomyelitis or extensive demyelination. Cells undergoing apoptosis were detected in the CNS of both the perforin (-/-) and control groups, indicating that perforin is not essential for programmed cell death. Neutralizing antibodies were not detected in either group of mice until day 9 postinfection, when the majority of the virus had been cleared. These data further confirm the importance of cell-mediated cytotoxicity and suggest that additional components of the immune response contribute to the clearance of JHMV from the CNS.