Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate
Herpes simplex virus 1 (HSV-1) gC is a multi-functional glycoprotein present in the viral envelope and on the surface of infected cells. Virion gC, and to a lesser extent the fusion protein gB, interacts with host heparan sulfate to mediate HSV-1 attachment to the cell surface. Virion gC selectively...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1549349/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849760899130195968 |
|---|---|
| author | Seth M. Schneider Seth M. Schneider Giulia Tebaldi Katrina A. Gianopulos Katrina A. Gianopulos Darin J. Weed Suzanne M. Pritchard Chloe Leach Anthony V. Nicola Anthony V. Nicola |
| author_facet | Seth M. Schneider Seth M. Schneider Giulia Tebaldi Katrina A. Gianopulos Katrina A. Gianopulos Darin J. Weed Suzanne M. Pritchard Chloe Leach Anthony V. Nicola Anthony V. Nicola |
| author_sort | Seth M. Schneider |
| collection | DOAJ |
| description | Herpes simplex virus 1 (HSV-1) gC is a multi-functional glycoprotein present in the viral envelope and on the surface of infected cells. Virion gC, and to a lesser extent the fusion protein gB, interacts with host heparan sulfate to mediate HSV-1 attachment to the cell surface. Virion gC selectively facilitates HSV-1 entry into cells that support entry by a low pH-dependent endocytic pathway. gC regulates fusion-associated conformational changes in gB. Here we investigated the mechanism by which gC plays a post-attachment role in HSV-1 entry into cells. HSV-1 entered HS-deficient cells by a low pH-dependent route. Similarly, HSV-1 deleted for HS-binding domains entered HS-bearing cells by a low pH pathway. Thus, the presence of HS on cells and the ability of HSV-1 to engage HS do not direct HSV-1 to a pH-dependent entry pathway. HSV-1 lacking gC accumulated in endosomes during viral entry, supporting the notion that gC influences viral penetration from endosomes. Interestingly, the pH-neutral cell–cell fusion mediated by HSV-1 glycoproteins gB, gD, and gH/gL was not altered by gC. Soluble heparin inhibited cell–cell fusion regardless of the presence of gC or heparan sulfate. The kinetics of endocytic uptake of gC-null HSV-1 was rapid and very similar to wild type virus. Thus, the role of gC in regulating low pH entry of HSV-1 occurs downstream of internalization of enveloped particles from the plasma membrane. Together, the results presented here and elsewhere support a post-attachment, post-internalization function for gC in HSV-1 entry that is independent of HS. |
| format | Article |
| id | doaj-art-4173834e9af7407a8195ea5c19554e00 |
| institution | DOAJ |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-4173834e9af7407a8195ea5c19554e002025-08-20T03:06:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-04-011610.3389/fmicb.2025.15493491549349Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfateSeth M. Schneider0Seth M. Schneider1Giulia Tebaldi2Katrina A. Gianopulos3Katrina A. Gianopulos4Darin J. Weed5Suzanne M. Pritchard6Chloe Leach7Anthony V. Nicola8Anthony V. Nicola9Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesSchool of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesSchool of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesSchool of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United StatesHerpes simplex virus 1 (HSV-1) gC is a multi-functional glycoprotein present in the viral envelope and on the surface of infected cells. Virion gC, and to a lesser extent the fusion protein gB, interacts with host heparan sulfate to mediate HSV-1 attachment to the cell surface. Virion gC selectively facilitates HSV-1 entry into cells that support entry by a low pH-dependent endocytic pathway. gC regulates fusion-associated conformational changes in gB. Here we investigated the mechanism by which gC plays a post-attachment role in HSV-1 entry into cells. HSV-1 entered HS-deficient cells by a low pH-dependent route. Similarly, HSV-1 deleted for HS-binding domains entered HS-bearing cells by a low pH pathway. Thus, the presence of HS on cells and the ability of HSV-1 to engage HS do not direct HSV-1 to a pH-dependent entry pathway. HSV-1 lacking gC accumulated in endosomes during viral entry, supporting the notion that gC influences viral penetration from endosomes. Interestingly, the pH-neutral cell–cell fusion mediated by HSV-1 glycoproteins gB, gD, and gH/gL was not altered by gC. Soluble heparin inhibited cell–cell fusion regardless of the presence of gC or heparan sulfate. The kinetics of endocytic uptake of gC-null HSV-1 was rapid and very similar to wild type virus. Thus, the role of gC in regulating low pH entry of HSV-1 occurs downstream of internalization of enveloped particles from the plasma membrane. Together, the results presented here and elsewhere support a post-attachment, post-internalization function for gC in HSV-1 entry that is independent of HS.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1549349/fullherpes simplex virusfusionglycoprotein Cheparan sulfatevirus entryvirus penetration |
| spellingShingle | Seth M. Schneider Seth M. Schneider Giulia Tebaldi Katrina A. Gianopulos Katrina A. Gianopulos Darin J. Weed Suzanne M. Pritchard Chloe Leach Anthony V. Nicola Anthony V. Nicola Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate Frontiers in Microbiology herpes simplex virus fusion glycoprotein C heparan sulfate virus entry virus penetration |
| title | Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate |
| title_full | Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate |
| title_fullStr | Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate |
| title_full_unstemmed | Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate |
| title_short | Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate |
| title_sort | herpes simplex virus 1 glycoprotein c promotes virus penetration from endosomes during entry independent of interaction with heparan sulfate |
| topic | herpes simplex virus fusion glycoprotein C heparan sulfate virus entry virus penetration |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1549349/full |
| work_keys_str_mv | AT sethmschneider herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT sethmschneider herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT giuliatebaldi herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT katrinaagianopulos herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT katrinaagianopulos herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT darinjweed herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT suzannempritchard herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT chloeleach herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT anthonyvnicola herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate AT anthonyvnicola herpessimplexvirus1glycoproteincpromotesviruspenetrationfromendosomesduringentryindependentofinteractionwithheparansulfate |