Arii Jun, Hirohata Yoshitaka, Kato Akihisa, Kawaguchi Yasushi
Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
J Virol. 2015 Feb;89(3):1879-88. doi: 10.1128/JVI.03079-14. Epub 2014 Nov 26.
Nonmuscle myosin heavy chain IIA (NMHC-IIA) has been reported to function as a herpes simplex virus 1 (HSV-1) entry coreceptor by interacting with viral envelope glycoprotein B (gB). Vertebrates have three genetically distinct isoforms of the NMHC-II, designated NMHC-IIA, NMHC-IIB, and NMHC-IIC. COS cells, which are readily infected by HSV-1, do not express NMHC-IIA but do express NMHC-IIB. This observation prompted us to investigate whether NMHC-IIB might associate with HSV-1 gB and be involved in an HSV-1 entry like NMHC-IIA. In these studies, we show that (i) NMHC-IIB coprecipitated with gB in COS-1 cells upon HSV-1 entry; (ii) a specific inhibitor of myosin light chain kinase inhibited cell surface expression of NMHC-IIB in COS-1 cells upon HSV-1 entry as well as HSV-1 infection, as reported with NMHC-IIA; (iii) overexpression of mouse NMHC-IIB in IC21 cells significantly increased their susceptibility to HSV-1 infection; and (iv) knockdown of NMHC-IIB in COS-1 cells inhibited HSV-1 infection as well as cell-cell fusion mediated by HSV-1 envelope glycoproteins. These results supported the hypothesis that, like NMHC-IIA, NMHC-IIB associated with HSV-1 gB and mediated HSV-1 entry.
Herpes simplex virus 1 (HSV-1) was reported to utilize nonmuscle myosin heavy chain IIA (NMHC-IIA) as an entry coreceptor associating with gB. Vertebrates have three genetically distinct isoforms of NMHC-II. In these isoforms, NMHC-IIB is of special interest since it highly expresses in neuronal tissue, one of the most important cellular targets of HSV-1 in vivo. In this study, we demonstrated that the ability to mediate HSV-1 entry appeared to be conserved in NMHC-II isoforms. These results may provide an insight into the mechanism by which HSV-1 infects a wide variety of cell types in vivo.
据报道，非肌肉肌球蛋白重链IIA（NMHC-IIA）通过与病毒包膜糖蛋白B（gB）相互作用，作为单纯疱疹病毒1（HSV-1）进入的共受体发挥作用。脊椎动物有三种基因不同的NMHC-II同工型，分别命名为NMHC-IIA、NMHC-IIB和NMHC-IIC。易被HSV-1感染的COS细胞不表达NMHC-IIA，但表达NMHC-IIB。这一观察结果促使我们研究NMHC-IIB是否可能与HSV-1 gB结合，并像NMHC-IIA一样参与HSV-1的进入过程。在这些研究中，我们发现：（i）HSV-1进入时，NMHC-IIB在COS-1细胞中与gB共沉淀；（ii）与NMHC-IIA的情况一样，肌球蛋白轻链激酶的特异性抑制剂抑制了HSV-1进入时COS-1细胞中NMHC-IIB的细胞表面表达以及HSV-1感染；（iii）在IC21细胞中过表达小鼠NMHC-IIB显著增加了它们对HSV-1感染的易感性；（iv）在COS-1细胞中敲低NMHC-IIB抑制了HSV-1感染以及由HSV-1包膜糖蛋白介导的细胞间融合。这些结果支持了这样的假设，即与NMHC-IIA一样，NMHC-IIB与HSV-1 gB结合并介导HSV-1进入。
据报道，单纯疱疹病毒1（HSV-1）利用非肌肉肌球蛋白重链IIA（NMHC-IIA）作为与gB结合的进入共受体。脊椎动物有三种基因不同的NMHC-II同工型。在这些同工型中，NMHC-IIB特别受关注，因为它在神经元组织中高度表达，而神经元组织是HSV-1在体内最重要的细胞靶点之一。在这项研究中，我们证明了介导HSV-1进入的能力在NMHC-II同工型中似乎是保守的。这些结果可能为深入了解HSV-1在体内感染多种细胞类型的机制提供线索。
