Protective and Pathologic Roles of the Immune Response to Mouse Hepatitis Virus Type 1: Implications for Severe Acute Respiratory Syndrome
Protective and Pathologic Roles of the Immune Response to Mouse Hepatitis Virus Type 1: Implications for Severe Acute Respiratory Syndrome
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DOI：
10.1128/jvi.00355-09
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发表时间：
2009-09-15
影响因子：
5.4
通讯作者：
Harty, John T.
中科院分区：
文献类型：
--
作者：
Khanolkar, Aaruni;Hartwig, Stacey M.;Harty, John T.
小鼠鼻内感染1型小鼠肝炎病毒（MHV-1）诱导的肺部病理学与严重急性呼吸综合征（SARS）患者相似。然而，MHV-1诱导的肺部疾病的严重程度在小鼠品系之间存在差异，并且已经表明宿主免疫应答的差异可能是这种差异的原因。免疫病理学可能是SARS的一个重要临床特征。关于宿主对MHV-1的免疫反应以及它如何导致感染小鼠中检测到的一些病理变化，我们知之甚少。在这项研究中，我们表明，一个完整的I型干扰素系统和适应性免疫反应所需的控制MHV-1复制和预防发病率和死亡率在耐药C57 BL/6 J小鼠感染后。NK细胞应答还有助于最大限度地降低C57 BL/6 J小鼠感染MHV-1后的疾病严重程度。在A/J和C3 H/HeJ小鼠，这是高度易感MHV-1诱导的疾病，我们证明，CD 4和CD 8 T细胞有助于在原发性感染的发病率，和记忆反应可以提高发病率和死亡率在随后的再暴露于MHV-1。然而，A/J和C3 H/HeJ小鼠的发病率可以通过在MHV-1感染前用免疫血清治疗来最小化。总的来说，我们的研究结果强调了宿主免疫反应在冠状病毒诱导的呼吸道疾病发病机制中的作用。
Intranasal mouse hepatitis virus type 1 (MHV-1) infection of mice induces lung pathology similar to that observed in severe acute respiratory syndrome (SARS) patients. However, the severity of MHV-1-induced pulmonary disease varies among mouse strains, and it has been suggested that differences in the host immune response might account for this variation. It has also been suggested that immunopathology may represent an important clinical feature of SARS. Little is known about the host immune response to MHV-1 and how it might contribute to some of the pathological changes detected in infected mice. In this study we show that an intact type I interferon system and the adaptive immune responses are required for controlling MHV-1 replication and preventing morbidity and mortality in resistant C57BL/6J mice after infection. The NK cell response also helps minimize the severity of illness following MHV-1 infection of C57BL/6J mice. In A/J and C3H/HeJ mice, which are highly susceptible to MHV-1-induced disease, we demonstrate that both CD4 and CD8 T cells contribute to morbidity during primary infection, and memory responses can enhance morbidity and mortality during subsequent reexposure to MHV-1. However, morbidity in A/J and C3H/HeJ mice can be minimized by treating them with immune serum prior to MHV-1 infection. Overall, our findings highlight the role of the host immune response in contributing to the pathogenesis of coronavirus-induced respiratory disease.