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Journal of virology2013; 87(10); 5937-5948; doi: 10.1128/JVI.03522-12

Glycoprotein H and α4β1 integrins determine the entry pathway of alphaherpesviruses.

Abstract: Herpesviruses enter cells either by direct fusion at the plasma membrane or from within endosomes, depending on the cell type and receptor(s). We investigated two closely related herpesviruses of horses, equine herpesvirus type 1 (EHV-1) and EHV-4, for which the cellular and viral determinants routing virus entry are unknown. We show that EHV-1 enters equine epithelial cells via direct fusion at the plasma membrane, while EHV-4 does so via an endocytic pathway, which is dependent on dynamin II, cholesterol, caveolin 1, and tyrosine kinase activity. Exchange of glycoprotein H (gH) between EHV-1 and EHV-4 resulted in rerouting of EHV-1 to the endocytic pathway, as did blocking of α4β1 integrins on the cell surface. Furthermore, a point mutation in the SDI integrin-binding motif of EHV-1 gH also directed EHV-1 to the endocytic pathway. Cumulatively, we show that viral gH and cellular α4β1 integrins are important determinants in the choice of alphaherpesvirus cellular entry pathways.
Publication Date: 2013-03-20 PubMed ID: 23514881PubMed Central: PMC3648174DOI: 10.1128/JVI.03522-12Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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

APA
Azab W, Lehmann MJ, Osterrieder N. (2013). Glycoprotein H and α4β1 integrins determine the entry pathway of alphaherpesviruses. J Virol, 87(10), 5937-5948. https://doi.org/10.1128/JVI.03522-12

Publication

ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 87
Issue: 10
Pages: 5937-5948

Researcher Affiliations

Azab, Walid
  • Institut für Virologie, Freie Universität Berlin, Berlin, Germany.
Lehmann, Maik J
    Osterrieder, Nikolaus

      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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