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Scientific reports2017; 7(1); 16656; doi: 10.1038/s41598-017-16804-5

Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions.

Abstract: The respiratory epithelium of humans and animals is frequently exposed to alphaherpesviruses, originating from either external exposure or reactivation from latency. To date, the polarity of alphaherpesvirus infection in the respiratory epithelium and the role of respiratory epithelial integrity herein has not been studied. Equine herpesvirus type 1 (EHV1), a well-known member of the alphaherpesvirus family, was used to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (EREC), grown at the air-liquid interface. EHV1 binding to and infection of mucosal explants was greatly enhanced upon destruction of the respiratory epithelium integrity with EGTA or N-acetylcysteine. EHV1 preferentially bound to and entered EREC at basolateral cell surfaces. Restriction of infection via apical inoculation was overcome by disruption of intercellular junctions. Finally, basolateral but not apical EHV1 infection of EREC was dependent on cellular N-linked glycans. Overall, our findings demonstrate that integrity of the respiratory epithelium is crucial in the host's innate defence against primary alphaherpesvirus infections. In addition, by targeting a basolaterally located receptor in the respiratory epithelium, alphaherpesviruses have generated a strategy to efficiently escape from host defence mechanisms during reactivation from latency.
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Publication Date: 2017-11-30 PubMed ID: 29192251PubMed Central: PMC5709510DOI: 10.1038/s41598-017-16804-5Google Scholar: Lookup
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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 investigates how the integrity of the respiratory epithelium, a barrier of tissue lining the respiratory tract, affects infection by alphaherpesviruses, using the example of equine herpesvirus type 1 (EHV1). The study indicates that infection is more efficient when the respiratory epithelium is disrupted and that the virus specifically targets a receptor located on the side of cells facing away from the lumen of the respiratory tract to bypass host defense mechanisms.

Methodology and Key Findings

  • The researchers used equine herpesvirus type 1(EHV1) to infect equine respiratory mucosal explants and primary equine respiratory epithelial cells (ERECs), which were grown at the air-liquid interface.
  • They observed an increased EHV1 binding to and infection of the explants upon the destruction of respiratory epithelium integrity, achieved through the use of EGTA or N-acetylcysteine.
  • The researchers found that EHV1 preferentially bound to and entered EREC at the basolateral cell surfaces, that is, the side of the epithelial cells facing away from the lumen of the respiratory tract.
  • The access of EHV1 to the cells via the apical surface, facing the lumen, was restricted and could only be overcome by disrupting the intercellular junctions that hold cells together.
  • Additionally, basolateral EHV1 infection of the EREC was dependent on cellular N-linked glycans, but not when the infection occurred apically.

Implication of the Research

  • The findings indicate that the integrity of the respiratory epithelium, the presence of an intact cell barrier, is crucial in defending against primary alphaherpesvirus infections.
  • Alphaherpesviruses have developed a strategy to efficiently escape the host’s defense mechanisms by specifically targeting a receptor located basolaterally in the respiratory epithelium during reactivation from latency.

Conclusion

  • The research contributes to better understanding of the entry mechanisms of alphaherpesviruses, their strategies to evade host defenses and the role of the respiratory epithelia as a barrier in viral infections.
  • The outcomes of the research could potentially help design better therapeutic targets and preventive strategies against alphaherpesvirus infections.

Cite This Article

APA
Van Cleemput J, Poelaert KCK, Laval K, Maes R, Hussey GS, Van den Broeck W, Nauwynck HJ. (2017). Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. Sci Rep, 7(1), 16656. https://doi.org/10.1038/s41598-017-16804-5

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 7
Issue: 1
Pages: 16656
PII: 16656

Researcher Affiliations

Van Cleemput, Jolien
  • Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Poelaert, Katrien C K
  • Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Laval, Kathlyn
  • Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, 119 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey, 08544, USA.
Maes, Roger
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, Michigan, 48824, USA.
Hussey, Gisela S
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, Michigan, 48824, USA.
Van den Broeck, Wim
  • Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Nauwynck, Hans J
  • Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. hans.nauwynck@ugent.be.

MeSH Terms

  • Alphaherpesvirinae / physiology
  • Animals
  • Herpesviridae Infections / veterinary
  • Herpesvirus 1, Equid / physiology
  • Horse Diseases / metabolism
  • Horse Diseases / virology
  • Horses
  • Intercellular Junctions / drug effects
  • Intercellular Junctions / metabolism
  • Polysaccharides / metabolism
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / virology
  • Viral Load
  • Virus Replication

Conflict of Interest Statement

The authors declare that they have no competing interests.

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