CD46 Is a Protein Receptor for Human Adenovirus Type 64
Certain species D human adenoviruses (HAdV-D19, -D37, and -D64) are causative agents of epidemic keratoconjunctivitis. HAdV-D37 has previously been shown to bind CD46 (membrane cofactor protein) and sialic acid as adhesion receptors. HAdV-D64 is genetically highly similar to HAdV-D37, with an identi...
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2024-11-01
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| author | Eugene Y. Wu Alexander M. Robertson Hanglin (Henry) Zhu Corina Stasiak Laura A. Murray-Nerger Emily Romanoff Jesse Woon Beth A. Bromme Jason G. Smith |
| author_facet | Eugene Y. Wu Alexander M. Robertson Hanglin (Henry) Zhu Corina Stasiak Laura A. Murray-Nerger Emily Romanoff Jesse Woon Beth A. Bromme Jason G. Smith |
| author_sort | Eugene Y. Wu |
| collection | DOAJ |
| description | Certain species D human adenoviruses (HAdV-D19, -D37, and -D64) are causative agents of epidemic keratoconjunctivitis. HAdV-D37 has previously been shown to bind CD46 (membrane cofactor protein) and sialic acid as adhesion receptors. HAdV-D64 is genetically highly similar to HAdV-D37, with an identical fiber protein sequence, but differs substantially in its penton base and hexon proteins, two other major capsid components, due to genetic recombination. Here, we demonstrate that, like HAdV-D37, HAdV-D64 virions bind directly to CD46 and that CD46 and sialic acid also function as receptors for HAdV-D64 on multiple cell types. Expression of CD46 on CD46-negative cells conferred susceptibility to HAdV-D64 entry. Specifically blocking HAdV-D64 binding to CD46 on the host cell surface strongly inhibits viral entry and gene delivery into multiple cell lines that represent target tissues. We show that CD46 is expressed on human conjunctival epithelial cells and directly binds to the HAdV-D64 virion. Our results suggest that HAdV-D64 may be used to deliver genes to target conjunctival cells and that interrupting HAdV-D64 entry through its interaction with CD46 may prevent or lessen adenovirus-associated ocular disease. |
| format | Article |
| id | doaj-art-058b545aa2b742ff93f390bba5ecc009 |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj-art-058b545aa2b742ff93f390bba5ecc0092025-08-20T02:43:46ZengMDPI AGViruses1999-49152024-11-011612182710.3390/v16121827CD46 Is a Protein Receptor for Human Adenovirus Type 64Eugene Y. Wu0Alexander M. Robertson1Hanglin (Henry) Zhu2Corina Stasiak3Laura A. Murray-Nerger4Emily Romanoff5Jesse Woon6Beth A. Bromme7Jason G. Smith8Department of Biology, University of Richmond, Richmond, VA 23173, USADepartment of Biology, University of Richmond, Richmond, VA 23173, USADepartment of Biology, University of Richmond, Richmond, VA 23173, USADepartment of Biology, University of Richmond, Richmond, VA 23173, USADepartment of Biology, University of Richmond, Richmond, VA 23173, USADepartment of Biology, University of Richmond, Richmond, VA 23173, USADepartment of Biology, University of Richmond, Richmond, VA 23173, USADepartment of Microbiology, University of Washington School of Medicine, Seattle, WA 98109, USADepartment of Microbiology, University of Washington School of Medicine, Seattle, WA 98109, USACertain species D human adenoviruses (HAdV-D19, -D37, and -D64) are causative agents of epidemic keratoconjunctivitis. HAdV-D37 has previously been shown to bind CD46 (membrane cofactor protein) and sialic acid as adhesion receptors. HAdV-D64 is genetically highly similar to HAdV-D37, with an identical fiber protein sequence, but differs substantially in its penton base and hexon proteins, two other major capsid components, due to genetic recombination. Here, we demonstrate that, like HAdV-D37, HAdV-D64 virions bind directly to CD46 and that CD46 and sialic acid also function as receptors for HAdV-D64 on multiple cell types. Expression of CD46 on CD46-negative cells conferred susceptibility to HAdV-D64 entry. Specifically blocking HAdV-D64 binding to CD46 on the host cell surface strongly inhibits viral entry and gene delivery into multiple cell lines that represent target tissues. We show that CD46 is expressed on human conjunctival epithelial cells and directly binds to the HAdV-D64 virion. Our results suggest that HAdV-D64 may be used to deliver genes to target conjunctival cells and that interrupting HAdV-D64 entry through its interaction with CD46 may prevent or lessen adenovirus-associated ocular disease.https://www.mdpi.com/1999-4915/16/12/1827adenovirusepidemic keratoconjunctivitisCD46membrane cofactor proteinreceptor |
| spellingShingle | Eugene Y. Wu Alexander M. Robertson Hanglin (Henry) Zhu Corina Stasiak Laura A. Murray-Nerger Emily Romanoff Jesse Woon Beth A. Bromme Jason G. Smith CD46 Is a Protein Receptor for Human Adenovirus Type 64 Viruses adenovirus epidemic keratoconjunctivitis CD46 membrane cofactor protein receptor |
| title | CD46 Is a Protein Receptor for Human Adenovirus Type 64 |
| title_full | CD46 Is a Protein Receptor for Human Adenovirus Type 64 |
| title_fullStr | CD46 Is a Protein Receptor for Human Adenovirus Type 64 |
| title_full_unstemmed | CD46 Is a Protein Receptor for Human Adenovirus Type 64 |
| title_short | CD46 Is a Protein Receptor for Human Adenovirus Type 64 |
| title_sort | cd46 is a protein receptor for human adenovirus type 64 |
| topic | adenovirus epidemic keratoconjunctivitis CD46 membrane cofactor protein receptor |
| url | https://www.mdpi.com/1999-4915/16/12/1827 |
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