Heparanase is a host enzyme required for herpes simplex virus-1 release from cells

Nat Commun. 2015 Apr 27;6:6985. doi: 10.1038/ncomms7985.

Abstract

Herpesviruses exemplified by herpes simplex virus-1 (HSV-1) attach to cell surface heparan sulfate (HS) for entry into host cells. However, during a productive infection, the HS moieties on parent cells can trap newly exiting viral progenies and inhibit their release. Here we demonstrate that a HS-degrading enzyme of the host, heparanase (HPSE), is upregulated through NF-kB and translocated to the cell surface upon HSV-1 infection for the removal of HS to facilitate viral release. We also find a significant increase in HPSE release in vivo during infection of murine corneas and that knockdown of HPSE in vivo inhibits virus shedding. Overall, we propose that HPSE acts as a molecular switch for turning a virus-permissive 'attachment mode' of host cells to a virus-deterring 'detachment mode'. Since many human viruses use HS as an attachment receptor, the HPSE-HS interplay may delineate a common mechanism for virus release.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Female
  • Glucuronidase / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Heparitin Sulfate / metabolism*
  • Herpes Simplex / enzymology*
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / physiology*
  • Host-Pathogen Interactions
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Up-Regulation
  • Vero Cells
  • Virion / physiology*
  • Virus Release

Substances

  • Heparitin Sulfate
  • heparanase
  • Glucuronidase