Measles Virus Selectively Blind to Signaling Lymphocytic Activation Molecule (SLAM; CD150) Is Attenuated and Induces Strong Adaptive Immune Responses in Rhesus Monkeys
Measles Virus Selectively Blind to Signaling Lymphocytic Activation Molecule (SLAM; CD150) Is Attenuated and Induces Strong Adaptive Immune Responses in Rhesus Monkeys
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DOI：
10.1128/jvi.02304-09
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发表时间：
2010-04-01
影响因子：
5.4
通讯作者：
Cattaneo, Roberto
中科院分区：
文献类型：
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作者：
Leonard, Vincent H. J.;Hodge, Gregory;Cattaneo, Roberto
信号淋巴细胞活化分子（SLAM; CD 150）是麻疹病毒（MV）的免疫细胞受体。为了评估SLAM-MV相互作用对病毒传播和发病机制的重要性，我们产生了选择性地不能识别人SLAM（SLAM盲）的野生型IC-B MV。该病毒与完全毒力的野生型IC-B毒株的不同之处在于附着蛋白血凝素的氨基酸533处的单个丙氨酸至丙氨酸取代，并且通过SLAM感染细胞的效率比同基因野生型毒株低约40倍。离体，该病毒以低水平感染原代淋巴细胞，与SLAM表达无关。当一组六只恒河猴（Macaca mulatta）鼻内接种SLAM盲病毒时，没有记录到临床症状。只有一只猴子在感染后早期有低水平的病毒血症，而对照组的所有宿主都有高水平的病毒血症。尽管最小的，如果有的话，病毒血症，所有六个主机产生的中和抗体滴度接近的控制猴子，而MV-定向细胞免疫达到的水平至少高达野生型感染的猴子。这些发现正式证明了有效的SLAM识别对于MV毒力和致病性是必要的。他们还表明，选择性SLAM盲野生型MV可以开发成疫苗载体。
The signaling lymphocytic activation molecule (SLAM; CD150) is the immune cell receptor for measles virus (MV). To assess the importance of the SLAM-MV interactions for virus spread and pathogenesis, we generated a wild-type IC-B MV selectively unable to recognize human SLAM (SLAM-blind). This virus differs from the fully virulent wild-type IC-B strain by a single arginine-to-alanine substitution at amino acid 533 of the attachment protein hemagglutinin and infects cells through SLAM about 40 times less efficiently than the isogenic wild-type strain. Ex vivo, this virus infects primary lymphocytes at low levels regardless of SLAM expression. When a group of six rhesus monkeys (Macaca mulatta) was inoculated intranasally with the SLAM-blind virus, no clinical symptoms were documented. Only one monkey had low-level viremia early after infection, whereas all the hosts in the control group had high viremia levels. Despite minimal, if any, viremia, all six hosts generated neutralizing antibody titers close to those of the control monkeys while MV-directed cellular immunity reached levels at least as high as in wild-type-infected monkeys. These findings prove formally that efficient SLAM recognition is necessary for MV virulence and pathogenesis. They also suggest that the selectively SLAM-blind wild-type MV can be developed into a vaccine vector.