Chronic viral infections. like those of humans with cytomegalovirus, human immunodeficiency virus (even when under antiretroviral therapy), and hepatitis C virus or those of mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13), result in immune dysfunction that predisposes the host to severe infections with unrelated pathogens. It is known that C57BL/6 (B6) mice are resistant to mousepox, a lethal disease caused by the orthopoxvirus ectromelia virus (ECTV), and that this resistance requires natural killer (NK) cells and other immune cells. We show that most B6 mice chronically infected with CL13 succumb to mousepox but that most of those that recovered from acute infection with the LCMV Armstrong (Arm) strain survive. We also show that B6 mice chronically infected with CL13 and those that recovered from Arm infection have a reduced frequency and a reduced number of NK cells. However, at steady state, NK cells in mice that have recovered from Arm infection mature normally and, in response to ECTV, get activated, become more mature, proliferate, and increase their cytotoxicity in vivo Conversely, in mice chronically infected with CL13, NK cells are immature and residually activated, and following ECTV infection, they do not mature, proliferate, or increase their cytotoxicity. Given the well-established importance of NK cells in resistance to mousepox, these data suggest that the NK cell dysfunction caused by CL13 persistence may contribute to the susceptibility of CL13-infected mice to mousepox. Whether chronic infections similarly affect NK cells in humans should be explored.IMPORTANCE Infection of adult mice with the clone 13 (CL13) strain of lymphocytic choriomeningitis virus (LCMV) is extensively used as a model of chronic infection. In this paper, we show that mice chronically infected with CL13 succumb to challenge with ectromelia virus (ECTV; the agent of mousepox) and that natural killer (NK) cells in CL13-infected mice are reduced in numbers and have an immature and partially activated phenotype but do respond to ECTV. These data may provide additional clues why humans chronically infected with certain pathogens are less resistant to viral diseases.

中文翻译：

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慢性淋巴细胞性脑膜炎感染导致对鼠痘的易感性，并损害自然杀伤细胞的成熟和功能。

慢性病毒感染。像患有巨细胞病毒，人类免疫缺陷病毒（即使在接受抗逆转录病毒疗法的情况下）和丙型肝炎病毒的人，或者患有淋巴细胞性脉络膜脑膜炎病毒（LCMV）克隆13（CL13）的小鼠的那些，都会导致免疫功能障碍，使宿主容易遭受严重感染与无关的病原体。已知C57BL / 6（B6）小鼠对鼠痘具有抵抗力，后者是由正痘病毒念珠菌病毒（ECTV）引起的致死性疾病，这种抵抗力需要自然杀伤（NK）细胞和其他免疫细胞。我们显示大多数慢性感染CL13的B6小鼠死于鼠痘，但是大多数从LCMV阿姆斯特朗（Arm）株急性感染中恢复的小鼠都可以存活。我们还显示，慢性感染CL13的B6小鼠和从Arm感染中恢复的B6小鼠的频率降低，NK细胞数量减少。但是，在稳定状态下，从Arm感染中恢复的小鼠中的NK细胞正常成熟，并且响应ECTV活化，变得更成熟，增殖并增加其体内细胞毒性。相反，在慢性感染CL13，NK的小鼠中细胞未成熟并残留活化，在ECTV感染后，它们不会成熟，增殖或增加细胞毒性。鉴于NK细胞对鼠痘的抵抗力已确立的重要性，这些数据表明，由CL13持久性引起的NK细胞功能障碍可能有助于CL13感染的小鼠对鼠痘的易感性。重要的是，应探索慢性感染是否同样会影响人类的NK细胞。重要事项淋巴细胞性脉络膜脑膜炎病毒（LCMV）的克隆13（CL13）株感染成年小鼠已被广泛用作慢性感染的模型。在本文中，我们表明，慢性感染CL13的小鼠会屈服于以念珠菌病毒（ECTV； mousepox的作用剂）攻击，而感染CL13的小鼠中的自然杀伤（NK）细胞数量减少，并且具有未成熟和部分活化的细胞表型，但确实对ECTV有反应。这些数据可能提供其他线索，说明为什么长期感染某些病原体的人对病毒疾病的抵抗力较低。在本文中，我们表明，慢性感染CL13的小鼠会屈服于以念珠菌病毒（ECTV； mousepox的作用剂）攻击，而感染CL13的小鼠中的自然杀伤（NK）细胞数量减少，并且具有未成熟和部分活化的细胞表型，但确实对ECTV有反应。这些数据可能提供其他线索，说明为什么长期感染某些病原体的人对病毒疾病的抵抗力较低。在本文中，我们表明，慢性感染CL13的小鼠会屈服于以念珠菌病毒（ECTV； mousepox的作用剂）攻击，而感染CL13的小鼠中的自然杀伤（NK）细胞数量减少，并且具有未成熟和部分活化的细胞表型，但确实对ECTV有反应。这些数据可能提供其他线索，说明为什么长期感染某些病原体的人对病毒疾病的抵抗力较低。