Measles virus infection of SLAM (CD150) knockin mice reproduces tropism and immunosuppression in human infection
Measles virus infection of SLAM (CD150) knockin mice reproduces tropism and immunosuppression in human infection
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DOI：
10.1128/jvi.02134-06
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Yanagi, Yusuke
中科院分区：
文献类型：
--
作者：
Ohno, Shinji;Ono, Nobuyuki;Yanagi, Yusuke
人信号淋巴细胞活化分子（SLAM，也称为CD 150）是抗原驱动的T细胞应答和巨噬细胞功能的调节剂，作为麻疹病毒（MV）的细胞受体，其V结构域是受体功能所必需和充分的。我们在这里报告了SLAM基因敲入小鼠的产生，其中小鼠SLAM的V结构域被人SLAM的V结构域取代。嵌合SLAM在敲入小鼠中具有预期的分布和正常功能。来自SLAM敲入小鼠的脾细胞允许强毒MV株的体外生长，但不允许Edmonston疫苗株的体外生长。与体外感染不同，NW只能在SLAM敲入小鼠中生长，这些小鼠也缺乏I型干扰素受体（IFNAR）。经腹腔或鼻内接种后，在脾脏和全身淋巴结中检测到MV，但在胸腺中未检测到MV。值得注意的是，鼻内接种后，病毒首先出现在纵隔淋巴结中。MV感染的IFNAR（-/-）SLAM敲入小鼠的脾细胞对伴刀豆球蛋白A的增殖反应受到抑制。因此，MV感染的SLAM基因敲入小鼠在人类感染中再现嗜淋巴细胞性和免疫抑制，作为麻疹的有用的小动物模型。
The human signaling lymphocyte activation molecule (SLAM, also called CD150), a regulator of antigen-driven T-cell responses and macrophage functions, acts as a cellular receptor for measles virus (MV), and its V domain is necessary and sufficient for receptor function. We report here the generation of SLAM knockin mice in which the V domain of mouse SLAM was replaced by that of human SLAM. The chimeric SLAM had an expected distribution and normal function in the knockin mice. Splenocytes from the SLAM knockin mice permitted the in vitro growth of a virulent MV strain but not that of the Edmonston vaccine strain. Unlike in vitro infection, NW could grow only in SLAM knockin mice that also lacked the type I interferon receptor (IFNAR). After intraperitoneal or intranasal inoculation, MV was detected in the spleen and lymph nodes throughout the body but not in the thymus. Notably, the virus appeared first in the mediastinal lymph node after intranasal inoculation. Splenocytes from MV-infected IFNAR(-/-) SLAM knockin mice showed suppression of proliferative responses to concanavalin A. Thus, MV infection of SLAM knockin mice reproduces lymphotropism and immunosuppression in human infection, serving as a useful small animal model for measles.