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


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.

SUBMITTER: Hadigal SR 

PROVIDER: S-EPMC4413471 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

Hadigal Satvik R SR   Agelidis Alex M AM   Karasneh Ghadah A GA   Antoine Thessicar E TE   Yakoub Abraam M AM   Ramani Vishnu C VC   Djalilian Ali R AR   Sanderson Ralph D RD   Shukla Deepak D  

Nature communications 20150427


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  ...[more]

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