Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1
Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1
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DOI：
10.1038/nature09420
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发表时间：
2010-10-14
期刊：
影响因子：
64.8
通讯作者：
Kawaguchi, Yasushi
中科院分区：
文献类型：
--
作者：
Arii, Jun;Goto, Hideo;Kawaguchi, Yasushi
单纯疱疹病毒 1 (HSV-1) 是α-疱疹病毒家族的原型，可导致人类终身感染。虽然 HSV-1 通常与各种皮肤粘膜疾病相关，但它也与致命性脑炎有关(1)。 HSV-1 进入宿主细胞需要包膜糖蛋白 B (gB) 和 D (gD) 的细胞受体(2-4)。然而，负责其广泛体外宿主范围和体内关键靶标感染的 gB 受体仍然未知。在这里，我们证明非肌肉肌球蛋白重链 IIA (NMHC-IIA) 是非肌肉肌球蛋白 IIA (NM-IIA) 的一个亚基，通过与 gB 相互作用充当 HSV-1 进入受体。当 NMHC-IIA 过表达时，对 HSV-1 感染具有相对抵抗力的细胞系 (5) 变得非常容易受到该病毒的感染。 NMHC-IIA 抗体可阻断自然允许的靶细胞中的 HSV-1 感染。此外，当 gB、gD、gH 和 gL 共表达时，允许细胞中 NMHC-IIA 的敲低抑制了 HSV-1 感染以及细胞与细胞的融合。在 HSV-1 进入的过程中，NMHC-IIA 的细胞表面表达被显着且快速地诱导。肌球蛋白轻链激酶的特异性抑制剂通过磷酸化调节 NM-IIA(6)，可减少细胞培养物和疱疹基质角膜炎鼠模型中 NMHC-IIA 的重新分布以及 HSV-1 感染。 NMHC-IIA 在各种人体组织和细胞类型中普遍表达 (7)，因此，它是一种功能性 gB 受体，在体外和体内介导广泛的 HSV-1 感染性。 NMHC-IIA 被鉴定为 HSV-1 进入受体，以及 NM-IIA 在 HSV-1 感染中的调节作用，为了解 HSV-1 进入提供了深入的了解，并确定了抗病毒药物开发的新靶点。
Herpes simplex virus-1 (HSV-1), the prototype of the a-herpesvirus family, causes life-long infections in humans. Although generally associated with various mucocutaneous diseases, HSV-1 is also involved in lethal encephalitis(1). HSV-1 entry into host cells requires cellular receptors for both envelope glycoproteins B (gB) and D (gD)(2-4). However, the gB receptors responsible for its broad host range in vitro and infection of critical targets in vivo1 remain unknown. Here we show that non-muscle myosin heavy chain IIA (NMHC-IIA), a subunit of non-muscle myosin IIA (NM-IIA), functions as an HSV-1 entry receptor by interacting with gB. A cell line that is relatively resistant to HSV-1 infection(5) became highly susceptible to infection by this virus when NMHC-IIA was overexpressed. Antibody to NMHC-IIA blocked HSV-1 infection in naturally permissive target cells. Furthermore, knockdown of NMHC-IIA in the permissive cells inhibited HSV-1 infection as well as cell-cell fusion when gB, gD, gH and gL were coexpressed. Cell-surface expression of NMHC-IIA was markedly and rapidly induced during the initiation of HSV-1 entry. A specific inhibitor of myosin light chain kinase, which regulates NM-IIA by phosphorylation(6), reduced the redistribution of NMHC-IIA as well as HSV-1 infection in cell culture and in a murine model for herpes stromal keratitis. NMHC-IIA is ubiquitously expressed in various human tissues and cell types(7) and, therefore, is implicated as a functional gB receptor that mediates broad HSV-1 infectivity both in vitro and in vivo. The identification of NMHC-IIA as an HSV-1 entry receptor and the involvement of NM-IIA regulation in HSV-1 infection provide an insight into HSV-1 entry and identify new targets for antiviral drug development.