Alpha/beta interferon protects against lethal west nile virus infection by restricting cellular tropism and enhancing neuronal survival
Alpha/beta interferon protects against lethal west nile virus infection by restricting cellular tropism and enhancing neuronal survival
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DOI：
10.1128/jvi.79.21.13350-13361.2005
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Diamond, MS
中科院分区：
文献类型：
--
作者：
Samuel, MA;Diamond, MS
西尼罗河病毒（WNV）是一种蚊子传播的黄病毒，在人类、鸟类和其他动物中嗜神经。虽然适应性免疫在防止西尼罗河病毒传播到中枢神经系统（CNS）方面发挥着重要作用，但对于α / β干扰素（ifn - α / β）如何保护外周和中枢神经系统感染知之甚少。在这项研究中，我们检测了西尼罗河病毒在ifn - α / β受体缺陷（ifn - α / β R-/-）小鼠和原代神经元培养中的毒力和嗜性。通过皮下接种ifn - α / β R-/-小鼠对WNV感染非常敏感，10(0)和10(2)PFU感染后死亡率为100%，平均死亡时间（MTD）分别为4.6 +/- 0.7和3.8 +/- 0.5天。相比之下，遗传野生型129Sv/Ev小鼠感染10(2)PFU后死亡率为62%，MTD为11.9 +/- 1.9天。在感染后的第3天，ifn - α / β R-/-小鼠在几乎所有检测组织中都出现了高病毒载量，包括野生型小鼠中许多未感染的组织。ifn - α / β R-/-小鼠也表现出细胞趋向性改变，脾脏巨噬细胞、B细胞和T细胞感染增加。此外，在感染前或感染后，体外用ifn - β处理原代野生型神经元可以增加神经元的存活，而不依赖于其对西尼罗河病毒复制的影响。总的来说，我们的数据表明，ifn - α / β通过限制趋向性和病毒负担以及防止感染神经元死亡来控制西尼罗河病毒感染。
West Nile virus (WNV) is a mosquito-borne flavivirus that is neurotropic in humans, birds, and other animals. While adaptive immunity plays an important role in preventing WNV spread to the central nervous system (CNS), little is known about how alpha/beta interferon (IFN-alpha/beta) protects against peripheral and CNS infection. In this study, we examine the virulence and tropism of WNV in IFN-alpha/beta receptor-deficient (IFN-alpha/beta R-/-) mice and primary neuronal cultures. IFN-alpha/beta R-/- mice were acutely susceptible to WNV infection through subcutaneous inoculation, with 100% mortality and a mean time to death (MTD) of 4.6 +/- 0.7 and 3.8 +/- 0.5 days after infection with 10(0) and 10(2) PFU, respectively. In contrast, congenic wild-type 129Sv/Ev mice infected with 10(2) PFU showed 62% mortality and a MTD of 11.9 +/- 1.9 days. IFN-alpha/beta R-/- mice developed high viral loads by day 3 after infection in nearly all tissues assayed, including many that were not infected in wild-type mice. IFN-alpha/beta R-/- mice also demonstrated altered cellular tropism, with increased infection in macrophages, B cells, and T cells in the spleen. Additionally, treatment of primary wild-type neurons in vitro with IFN-beta either before or after infection increased neuronal survival independent of its effect on WNV replication. Collectively, our data suggest that IFN-alpha/beta controls WNV infection by restricting tropism and viral burden and by preventing death of infected neurons.