Bukowski J F, Woda B A, Welsh R M
J Virol. 1984 Oct;52(1):119-28. doi: 10.1128/JVI.52.1.119-128.1984.
The effect of natural killer (NK) cells on the course of acute and persistent murine cytomegalovirus (MCMV) infection was examined by selectively depleting NK cell activity by inoculation of mice with antibody to asialo GM1, a neutral glycosphingolipid present at high concentrations on NK cells. The dose of MCMV required to cause 50% mortality or morbidity in control C57BL/6 mice dropped 4- and greater than 11-fold, respectively, in mice first treated with anti-asialo GM1. NK cell-depleted mice had higher (up to 1,000-fold) virus titers in their lungs, spleens, and livers at days 3, 5, 7, and 9 postinfection. Spleens and livers of control mice were virus-free by day 7 postinfection, and their lungs showed no signs of active infection at any time. In contrast, MCMV had disseminated to the lungs of NK cell-depleted mice by day 5, and these mice still had moderate levels of virus in their lungs, spleens, and livers at day 9. Markedly severe pathological changes were noted in the livers and spleens of NK cell-depleted, MCMV-infected mice. These included ballooning degeneration of hepatocytes and spleen necrosis. MCMV-infected, NK cell-depleted mice had severe spleen leukopenia, and their spleen leukocytes exhibited a significantly lower (up to 13-fold) response to the T cell mitogen concanavalin A when compared with those of uninfected and MCMV-infected controls. It appeared that NK cells exerted their most potent antiviral effect early in the infection, in a pattern correlating with interferon production and NK cell activation; treatment with anti-asialo GM1 later in infection had no effect on virus titers. The relative effect of NK cell depletion on MCMV pathogenesis depended on the injection route of the virus. NK cell depletion greatly augmented MCMV synthesis and pathogenesis in mice inoculated either intravenously or intraperitoneally but had no effect on the course of disease after intranasal inoculation, at any time point examined. One month after intraperitoneal inoculation of virus, NK cell depletion resulted in a six- to eightfold increase in salivary gland virus titers in persistently infected mice, suggesting that NK cells may be important in controlling virus synthesis in the salivary gland during persistent infection. This treatment did not, however, induce dissemination of virus to other organs. These data support the hypothesis that NK cells limit the severity, extent, and duration of acute MCMV infection and that they may also be involved in regulating the persistent infection.
通过给小鼠接种抗唾液酸GM1抗体（一种在自然杀伤（NK）细胞上高浓度存在的中性糖鞘脂）来选择性地降低NK细胞活性，从而研究NK细胞对急性和持续性小鼠巨细胞病毒（MCMV）感染病程的影响。在先用抗唾液酸GM1处理的小鼠中，导致对照C57BL/6小鼠50%死亡或发病所需的MCMV剂量分别下降了4倍和超过11倍。在感染后第3、5、7和9天，NK细胞耗竭的小鼠在其肺、脾和肝脏中的病毒滴度更高（高达1000倍）。感染后第7天，对照小鼠的脾和肝无病毒，且其肺在任何时候均无活跃感染迹象。相比之下，到感染后第5天，MCMV已扩散至NK细胞耗竭小鼠的肺，且这些小鼠在第9天时肺、脾和肝脏中仍有中等水平的病毒。在NK细胞耗竭的MCMV感染小鼠的肝和脾中观察到明显严重的病理变化。这些变化包括肝细胞气球样变性和脾坏死。MCMV感染的NK细胞耗竭小鼠有严重的脾白细胞减少，与未感染和MCMV感染的对照相比，其脾白细胞对T细胞有丝分裂原刀豆球蛋白A的反应显著降低（高达13倍）。似乎NK细胞在感染早期发挥其最有效的抗病毒作用，其模式与干扰素产生和NK细胞活化相关；在感染后期用抗唾液酸GM1处理对病毒滴度无影响。NK细胞耗竭对MCMV发病机制的相对影响取决于病毒的注射途径。NK细胞耗竭极大地增强了经静脉或腹腔接种的小鼠中的MCMV合成和发病机制，但在鼻内接种后的任何时间点对疾病病程均无影响。在腹腔接种病毒1个月后，NK细胞耗竭导致持续感染小鼠唾液腺病毒滴度增加6至8倍，这表明NK细胞在持续感染期间控制唾液腺病毒合成中可能很重要。然而，这种处理并未诱导病毒扩散至其他器官。这些数据支持以下假设：NK细胞限制急性MCMV感染的严重程度、范围和持续时间，并且它们可能也参与调节持续性感染。
