Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1

作者：Arii Jun; Goto Hideo; Suenaga Tadahiro; Oyama Masaaki; Kozuka Hata Hiroko; Imai Takahiko; Minowa Atsuko; Akashi Hiroomi; Arase Hisashi; Kawaoka Yoshihiro; Kawaguchi Yasushi^*

来源：Nature, 2010, 467(7317): 859-U129.

DOI：10.1038/nature09420

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.

• 出版日期2010-10-14
• 单位河北医科大学