Heparanase is a host enzyme required for herpes simplex virus-1 release from cells.
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.
Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, Illinois 60612, USA.
Satvik R
SR
Hadigal
1] Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, Illinois 60612, USA [2] Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, E-704 Medical Sciences Building, M/C 790, 835 South Wolcott Avenue, Chicago, Illinois 60612, USA.
Alex M
AM
Agelidis
1] Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, Illinois 60612, USA [2] Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, E-704 Medical Sciences Building, M/C 790, 835 South Wolcott Avenue, Chicago, Illinois 60612, USA.
Ghadah A
GA
Karasneh
1] Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, Illinois 60612, USA [2] Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, E-704 Medical Sciences Building, M/C 790, 835 South Wolcott Avenue, Chicago, Illinois 60612, USA.
Thessicar E
TE
Antoine
1] Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, Illinois 60612, USA [2] Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, E-704 Medical Sciences Building, M/C 790, 835 South Wolcott Avenue, Chicago, Illinois 60612, USA.
Abraam M
AM
Yakoub
Department of Pathology, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, Alabama 35294, USA.
Vishnu C
VC
Ramani
Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, Illinois 60612, USA.
Ali R
AR
Djalilian
Department of Pathology, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, Alabama 35294, USA.
Ralph D
RD
Sanderson
1] Ocular Virology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, M/C 648, Chicago, Illinois 60612, USA [2] Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, E-704 Medical Sciences Building, M/C 790, 835 South Wolcott Avenue, Chicago, Illinois 60612, USA.
Deepak
D
Shukla
D000818:Animals; D002522:Chlorocebus aethiops; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006497:Heparan Sulfate / Q000378:metabolism*; D006561:Herpes Simplex / Q000201:enzymology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015854:Up-Regulation; D014709:Vero Cells; D014771:Virion / Q000502:physiology*; D057074:Virus Release; D000099175:Heparanase
D005966:Glucuronidase; D006497:Heparan Sulfate; D000099175:Heparanase