Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus
Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus
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DOI：
10.1128/jvi.79.17.11300-11310.2005
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Weaver, SC
中科院分区：
文献类型：
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作者：
Aguilar, PV;Paessler, S;Weaver, SC
东部马脑炎病毒（EEEV）在北美（NA）引起人类脑炎，但在南美（SA）很少与人类疾病相关，这表明SA毒株的毒力较低。要评估的假设，这种毒力的差异是由于NA菌株逃避先天免疫的能力更大，我们比较了复制的NA和SA菌株在Vero细胞用干扰素（IFN）预处理。人IFN-α、IFN-β和IFN-γ对NA复制的影响一般小于SA株，支持这一假设。在小鼠模型中，NA和SA菌株之间未观察到IFN诱导的一致差异。在感染大多数EEEV毒株后，在IFN-α/β受体缺陷的小鼠中观察到比野生型小鼠更高的病毒血症水平和更短的存活时间，表明IFN-α/β在控制复制中很重要。与此相反，IFN-γ受体缺陷小鼠感染NA和SA株有类似的病毒血症水平和死亡率的野生型小鼠，表明IFN-γ不发挥主要作用，在鼠保护。小鼠预处理与聚（I-C），一种非特异性IFN诱导剂，表现出剂量依赖性的保护，对致命的东部马脑炎，进一步的证据表明，IFN是重要的控制疾病。总体而言，我们的体内结果不支持NA菌株在人体中更具毒性的假设，因为它们具有更强的对抗IFN应答的能力。然而，需要使用更好的人类疾病模型进行进一步研究，以确认在我们的体外实验中获得的差异人IFN敏感性的结果。
Eastern equine encephalitis virus (EEEV) causes human encephalitis in North America (NA), but in South America (SA) it has rarely been associated with human disease, suggesting that SA strains are less virulent. To evaluate the hypothesis that this virulence difference is due to a greater ability of NA strains to evade innate immunity, we compared replication of NA and SA strains in Vero cells pretreated with interferon (IFN). Human IFN-alpha, -beta, and -gamma generally exhibited less effect on replication of NA than SA strains, supporting this hypothesis. In the murine model, no consistent difference in IFN induction was observed between NA and SA strains. After infection with most EEEV strains, higher viremia levels and shorter survival times were observed in mice deficient in IFN-alpha/beta receptors than in wild-type mice, suggesting that IFN-alpha/beta is important in controlling replication. In contrast, IFN-gamma receptor-deficient mice infected with NA and SA strains had similar viremia levels and mortality rates to those of wild-type mice, suggesting that IFN-gamma does not play a major role in murine protection. Mice pretreated with poly(I-C), a nonspecific IFN inducer, exhibited dose-dependent protection against fatal eastern equine encephalitis, further evidence that IFN is important in controlling disease. Overall, our in vivo results did not support the hypothesis that NA strains are more virulent in humans due to their greater ability to counteract the IFN response. However, further studies using a better model of human disease are needed to confirm the results of differential human IFN sensitivity obtained in our in vitro experiments.