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CD46 Is a Protein Receptor for Human Adenovirus Type 64
Eugene Y Wu1, Alexander M Robertson1, Hanglin Henry Zhu1
1Department of Biology, University of Richmond, Richmond, VA 23173, USA.
Abstract:
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.
Insights
Human adenovirus D64 (HAdV-D64) uses CD46 and sialic acid as receptors for cell entry, similar to HAdV-D37. Blocking this interaction may prevent HAdV-D64-associated eye infections.
Area of Science:
- Virology
- Ophthalmology
- Cell Biology
Background:
- Certain human adenovirus D species (HAdV-D19, -D37, -D64) cause epidemic keratoconjunctivitis.
- HAdV-D37 utilizes CD46 (membrane cofactor protein) and sialic acid as cellular receptors.
- HAdV-D64 shares genetic similarity with HAdV-D37 but differs in key capsid proteins due to recombination.
Purpose of the Study:
- To investigate the cellular receptors used by HAdV-D64 for viral entry.
- To determine if CD46 and sialic acid function as receptors for HAdV-D64.
- To explore the potential of HAdV-D64 for gene delivery and therapeutic interventions in ocular diseases.
Main Methods:
- Binding assays to assess HAdV-D64 interaction with CD46 and sialic acid.
- Cell culture experiments using CD46-expressing and CD46-negative cells.
- Inhibition studies blocking HAdV-D64 binding to CD46.
- Analysis of CD46 expression on human conjunctival epithelial cells.
Main Results:
- HAdV-D64 virions bind directly to CD46, functioning as a receptor.
- CD46 and sialic acid serve as adhesion receptors for HAdV-D64 on various cell types.
- Expression of CD46 confers susceptibility to HAdV-D64 entry in CD46-negative cells.
- Blocking HAdV-D64-CD46 interaction significantly inhibits viral entry and gene delivery.
- CD46 is expressed on human conjunctival epithelial cells and binds HAdV-D64.
Conclusions:
- HAdV-D64 utilizes CD46 and sialic acid as key receptors for cellular entry.
- CD46 expression on conjunctival cells suggests a role in HAdV-D64 ocular infections.
- Targeting the HAdV-D64-CD46 interaction offers a potential strategy for preventing or treating adenovirus-associated ocular diseases.
- HAdV-D64 holds potential for targeted gene delivery to conjunctival cells.
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