Canine distemper virus with the intact C protein has the potential to replicate in human epithelial cells by using human nectin4 as a receptor

Canine distemper virus with the intact C protein has the potential to replicate in human epithelial cells by using human nectin4 as a receptor
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DOI:
10.1016/j.virol.2012.10.033
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发表时间:
2013-01-20
期刊:
影响因子:
3.7
通讯作者:
Takeda, Makoto
Takeda, Makoto
中科院分区:
医学3区
文献类型:
--
作者:
Otsuki, Noriyuki;Sekizuka, Tsuyoshi;Takeda, Makoto

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最近在猴子身上爆发的疫情已经证明,犬瘟热病毒(CDV)会导致多种哺乳动物患病。 CDV 使用 SLAM 和 nectin4 作为受体在易感动物中复制。在这里,我们证明人类 nectin4(而非人类 SLAM)具有作为 CDV 受体的完整功能。 CDV Ac96I 菌株在表达 nectin4 的人上皮 NCI-H358 细胞中几乎无法复制,但很容易适应在其中生长。毫不奇怪,H 蛋白中的氨基酸不需要改变来适应。原始Ac96I菌株具有截短的C蛋白,在NCI-H358细胞中生长后选择具有完整C蛋白的亚群。具有完整 C 蛋白的其他 CDV 菌株在 NCI-H358 细胞中表现出比具有截短 C 蛋白的 Ac96I 菌株显着更高的生长能力。这些发现表明,C 蛋白在人上皮细胞中具有功能,并且对于 CDV 在其中的复制至关重要。 (C) 2012 Elsevier Inc. 保留所有权利。
Recent outbreaks in monkeys have proven that canine distemper virus (CDV) causes diseases in a wide range of mammals. CDV uses SLAM and nectin4 as receptors to replicate in susceptible animals. Here, we show that human nectin4, but not human SLAM, is fully functional as a CDV receptor. The CDV Ac96I strain hardly replicated in nectin4-expressing human epithelial NCI-H358 cells, but readily adapted to grow in them. Unsurprisingly, no amino acid change in the H protein was required for the adaptation. The original Ac96I strain possessed a truncated C protein, and a subpopulation possessing the intact C protein was selected after growth in NCI-H358 cells. Other CDV strains possessing the intact C protein showed significantly higher growth abilities in NCI-H358 cells than the Ac96I strain with the truncated C protein. These findings suggest that the C protein is functional in human epithelial cells and critical for CDV replication in them. (C) 2012 Elsevier Inc. All rights reserved.