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

Nature. 2010 Oct 14;467(7317):859-62. doi: 10.1038/nature09420.


Herpes simplex virus-1 (HSV-1), the prototype of the α-herpesvirus family, causes life-long infections in humans. Although generally associated with various mucocutaneous diseases, HSV-1 is also involved in lethal encephalitis. HSV-1 entry into host cells requires cellular receptors for both envelope glycoproteins B (gB) and D (gD). However, the gB receptors responsible for its broad host range in vitro and infection of critical targets in vivo 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 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, 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Animals
  • Azepines / pharmacology
  • CHO Cells
  • Cell Fusion
  • Chlorocebus aethiops
  • Cricetinae
  • Cricetulus
  • Female
  • Gene Knockdown Techniques
  • HEK293 Cells
  • HL-60 Cells
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / metabolism
  • Herpesvirus 1, Human / physiology*
  • Humans
  • Mice
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Naphthalenes / pharmacology
  • Nonmuscle Myosin Type IIA / deficiency
  • Nonmuscle Myosin Type IIA / genetics
  • Nonmuscle Myosin Type IIA / metabolism*
  • Receptors, Virus / metabolism*
  • Temperature
  • Up-Regulation
  • Vero Cells
  • Viral Envelope Proteins / metabolism
  • Virus Internalization / drug effects


  • Azepines
  • Naphthalenes
  • Receptors, Virus
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus
  • ML 7
  • Myosin-Light-Chain Kinase
  • Nonmuscle Myosin Type IIA