MDA5 and MAVS Mediate Type I Interferon Responses to Coxsackie B Virus
MDA5 and MAVS Mediate Type I Interferon Responses to Coxsackie B Virus
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DOI：
10.1128/jvi.00631-09
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发表时间：
2010-01-01
影响因子：
5.4
通讯作者：
Finberg, Robert W.
中科院分区：
文献类型：
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作者：
Wang, Jennifer P.;Cerny, Anna;Finberg, Robert W.
科萨基B病毒（CVB）是与多种人类疾病（包括心肌炎）相关的肠道病毒。在本研究中，我们发现MDA5及其衔接分子MAVS对于I型干扰素对CVB的应答是至关重要的，因为MAVS或MDA5的缺失导致感染CVB的小鼠中I型干扰素产生缺陷和早期死亡。MAVS和MDA5基因敲除小鼠感染CVB后，病理组织学检查可见胰腺和肝脏坏死。响应于系统性CVB感染的炎性细胞因子产生独立于MAVS。令人惊讶的是，尽管I型干扰素水平显著降低，但MAVS缺陷小鼠的病毒滴度并未升高。这些数据突出了I型干扰素在宿主防御中的重要性，并提供了对柯萨奇病毒感染后先天免疫反应机制的见解。
Coxsackie B viruses (CVB) are enteroviruses that have been associated with a variety of human diseases, including myocarditis. In the present study, we found that MDA5 and its adaptor molecule MAVS are critical for type I interferon responses to CVB, since the absence of either MAVS or MDA5 leads to deficient type I interferon production and early mortality in mice infected with CVB. Pancreatic and hepatic necrosis were observed on histopathological examination of MAVS and MDA5 knockout mice infected with CVB. Inflammatory cytokine production in response to systemic CVB infection was independent of MAVS. Surprisingly, virus titers were not elevated in MAVS-deficient mice, despite significant reductions in type I interferon levels. These data highlight the importance of type I interferon in host defense and provide insight on the mechanisms of innate immune responses following coxsackievirus infection.