Glycoprotein H and α4β1 integrins determine the entry pathway of alphaherpesviruses.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
The research article investigates how two closely related horse herpesviruses enter cells. It reveals that the viral glycoprotein H and cellular alpha4beta1 integrins significantly determine the chosen pathway for alphaherpesvirus cellular entry.
Research Background
Herpesviruses, including equine herpesvirus type 1 (EHV-1) and EHV-4 that affect horses, can enter cells through different pathways. These may involve direct fusion at the plasma membrane or internalization via endosomes. The choice of entry depends on multiple factors, including the type of cell and the presence of receptors. However, for EHV-1 and EHV-4, the determinants influencing the virus entry route have not been previously identified.
Methodology and Findings
- The researchers examined how EHV-1 and EHV-4 enter equine epithelial cells. They found that EHV-1 fuses directly with the plasma membrane while EHV-4 enters via an endocytic pathway.
- They discovered that the EHV-4 pathway was dependent on dynamin II (a large GTPase protein), cholesterol, caveolin 1 (a protein involved in caveolae formation), and tyrosine kinase activity (linked to signal transduction).
- By exchanging the glycoprotein H (gH) between EHV-1 and EHV-4, they re-routed EHV-1 to the endocytic pathway, displaying the significant role of glycoprotein H in determining the entry pathway for the virus.
- Moreover, blocking alpha4beta1 integrins on the cell surface also redirected EHV-1 to the endocytic pathway. These integrins are cellular proteins that contribute to cell adhesion.
- An induced point mutation in the SDI integrin-binding motif of EHV-1 glycoprotein H also directed EHV-1 to follow the endocytic entry route.
Conclusions
The study concludes that viral glycoprotein H and cellular alpha4beta1 integrins significantly influence the selected route of alphaherpesvirus cellular entry. It suggests these two elements as major determinant factors. Understanding these processes can offer valuable insights into the mechanisms of herpesvirus infectivity, providing potential targets for antiviral strategies.
Cite This Article
Publication
Researcher Affiliations
- Institut für Virologie, Freie Universität Berlin, Berlin, Germany.
MeSH Terms
- Animals
- Cell Line
- Herpesvirus 1, Equid / physiology
- Herpesvirus 4, Equid / physiology
- Horses
- Host-Pathogen Interactions
- Integrin alpha4beta1 / metabolism
- Viral Envelope Proteins / metabolism
- Virus Internalization
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Citations
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