Protease, Growth Factor, and Heparanase-Mediated Syndecan-1 Shedding Leads to Enhanced HSV-1 Egress
Heparan sulfate (HS) and heparan sulfate proteoglycans (HSPGs) are considered important for the entry of many different viruses. Previously, we demonstrated that heparanase (HPSE), the host enzyme responsible for cleaving HS chains, is upregulated by herpes simplex virus-1 (HSV-1) infection. Higher...
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2021-09-01
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| Online Access: | https://www.mdpi.com/1999-4915/13/9/1748 |
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| author | Ghadah A. Karasneh Divya Kapoor Navya Bellamkonda Chandrashekhar D. Patil Deepak Shukla |
| author_facet | Ghadah A. Karasneh Divya Kapoor Navya Bellamkonda Chandrashekhar D. Patil Deepak Shukla |
| author_sort | Ghadah A. Karasneh |
| collection | DOAJ |
| description | Heparan sulfate (HS) and heparan sulfate proteoglycans (HSPGs) are considered important for the entry of many different viruses. Previously, we demonstrated that heparanase (HPSE), the host enzyme responsible for cleaving HS chains, is upregulated by herpes simplex virus-1 (HSV-1) infection. Higher levels of HPSE accelerate HS removal from the cell surface, facilitating viral release from infected cells. Here, we study the effects of overexpressing HPSE on viral entry, cell-to-cell fusion, plaque formation, and viral egress. We provide new information that higher levels of HPSE reduce syncytial plaque formation while promoting egress and extracellular release of the virions. We also found that transiently enhanced expression of HPSE did not affect HSV-1 entry into host cells or HSV-1-induced cell-to-cell fusion, suggesting that HPSE activation is tightly regulated and facilitates extracellular release of the maturing virions. We demonstrate that an HSPG-shedding agonist, PMA; a protease, thrombin; and a growth factor, EGF as well as bacterially produced recombinant heparinases resulted in enhanced HSV-1 release from HeLa and human corneal epithelial (HCE) cells. Our findings here underscore the significance of syndecan-1 functions in the HSV-1 lifecycle, provide evidence that the shedding of syndecan-1 ectodomain is another way HPSE works to facilitate HSV-1 release, and add new evidence on the significance of various HSPG shedding agonists in HSV-1 release from infected cells. |
| first_indexed | 2024-03-10T07:08:22Z |
| format | Article |
| id | doaj.art-1ed2afad8cbd41caa02581f2812ff344 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T07:08:22Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-1ed2afad8cbd41caa02581f2812ff3442023-11-22T15:37:23ZengMDPI AGViruses1999-49152021-09-01139174810.3390/v13091748Protease, Growth Factor, and Heparanase-Mediated Syndecan-1 Shedding Leads to Enhanced HSV-1 EgressGhadah A. Karasneh0Divya Kapoor1Navya Bellamkonda2Chandrashekhar D. Patil3Deepak Shukla4Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 835 S. Wolcott, Chicago, IL 60612, USADepartment of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 835 S. Wolcott, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, 1855 W. Taylor, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, 1855 W. Taylor, Chicago, IL 60612, USADepartment of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 835 S. Wolcott, Chicago, IL 60612, USAHeparan sulfate (HS) and heparan sulfate proteoglycans (HSPGs) are considered important for the entry of many different viruses. Previously, we demonstrated that heparanase (HPSE), the host enzyme responsible for cleaving HS chains, is upregulated by herpes simplex virus-1 (HSV-1) infection. Higher levels of HPSE accelerate HS removal from the cell surface, facilitating viral release from infected cells. Here, we study the effects of overexpressing HPSE on viral entry, cell-to-cell fusion, plaque formation, and viral egress. We provide new information that higher levels of HPSE reduce syncytial plaque formation while promoting egress and extracellular release of the virions. We also found that transiently enhanced expression of HPSE did not affect HSV-1 entry into host cells or HSV-1-induced cell-to-cell fusion, suggesting that HPSE activation is tightly regulated and facilitates extracellular release of the maturing virions. We demonstrate that an HSPG-shedding agonist, PMA; a protease, thrombin; and a growth factor, EGF as well as bacterially produced recombinant heparinases resulted in enhanced HSV-1 release from HeLa and human corneal epithelial (HCE) cells. Our findings here underscore the significance of syndecan-1 functions in the HSV-1 lifecycle, provide evidence that the shedding of syndecan-1 ectodomain is another way HPSE works to facilitate HSV-1 release, and add new evidence on the significance of various HSPG shedding agonists in HSV-1 release from infected cells.https://www.mdpi.com/1999-4915/13/9/1748heparan sulfateheparan sulfate proteoglycanHSV-1 |
| spellingShingle | Ghadah A. Karasneh Divya Kapoor Navya Bellamkonda Chandrashekhar D. Patil Deepak Shukla Protease, Growth Factor, and Heparanase-Mediated Syndecan-1 Shedding Leads to Enhanced HSV-1 Egress Viruses heparan sulfate heparan sulfate proteoglycan HSV-1 |
| title | Protease, Growth Factor, and Heparanase-Mediated Syndecan-1 Shedding Leads to Enhanced HSV-1 Egress |
| title_full | Protease, Growth Factor, and Heparanase-Mediated Syndecan-1 Shedding Leads to Enhanced HSV-1 Egress |
| title_fullStr | Protease, Growth Factor, and Heparanase-Mediated Syndecan-1 Shedding Leads to Enhanced HSV-1 Egress |
| title_full_unstemmed | Protease, Growth Factor, and Heparanase-Mediated Syndecan-1 Shedding Leads to Enhanced HSV-1 Egress |
| title_short | Protease, Growth Factor, and Heparanase-Mediated Syndecan-1 Shedding Leads to Enhanced HSV-1 Egress |
| title_sort | protease growth factor and heparanase mediated syndecan 1 shedding leads to enhanced hsv 1 egress |
| topic | heparan sulfate heparan sulfate proteoglycan HSV-1 |
| url | https://www.mdpi.com/1999-4915/13/9/1748 |
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