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Veterinary pathology2019; 56(5); 703-710; doi: 10.1177/0300985819834616

Exogenous Expression of Equine MHC Class I Molecules in Mice Increases Susceptibility to Equine Herpesvirus 1 Pulmonary Infection.

Abstract: Equine herpesvirus 1 (EHV-1) uses equine major histocompatibility complex class I (MHC class I) as an entry receptor. Exogenous expression of equine MHC class I genes in murine cell lines confers susceptibility to EHV-1 infection. To examine the in vivo role of equine MHC class I as an entry receptor for EHV-1, we generated transgenic (Tg) mice expressing equine MHC class I under the control of the CAG promoter. Equine MHC class I protein was expressed in the liver, spleen, lung, and brain of Tg mice, which was confirmed by Western blot. However, equine MHC class I antigen was only detected in bronchiolar epithelium and not in other tissues, using the immunofluorescence method employed in this study. Both Tg and wild-type (WT) mice developed pneumonia 3 days after intranasal infection with EHV-1. The bronchiolar epithelial cells of Tg mice showed more severe necrosis, compared with those in WT mice. In addition, the number of virus antigen-positive cells in the lungs was higher in Tg mice than in WT mice. These results suggest that exogenous expression of equine MHC class I renders mice more susceptible to EHV-1 infection.
Publication Date: 2019-03-13 PubMed ID: 30866742DOI: 10.1177/0300985819834616Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research study explores how the introduction of horse genes related to immune response makes mice more susceptible to a horse-specific virus called Equine herpesvirus 1 (EHV-1).

Objective of the Study

  • The research aimed to understand the role of the horse’s Major Histocompatibility complex class I (MHC class I) as an initial receptor for EHV-1 infection by introducing these genes in a mouse model.

Methodology

  • The researchers created transgenic (Tg) mice that expressed the horse MHC class I gene, controlled by a CAG promoter.
  • This gene was expressed in the liver, spleen, lung, and brain of the Tg mice, which was validated through a Western blot analysis.
  • The MHC class I antigen, however, could only be seen in the bronchiolar epithelium, as shown using an immunofluorescence-based method.

Infection and Observation

  • Both Tg and normal mice (wild-type or WT) were exposed to EHV-1 infection through the nose. Post three days of exposure, all mice developed pneumonia.
  • However, the Tg mice showed more severe damage in their bronchiolar epithelial cells compared to the WT mice.

Results and Conclusion

  • Moreover, the count of cells in the lungs with positive virus antigens was higher in the Tg mice compared to the WT mice.
  • This lead to the conclusion that the introduction of horse MHC class I genes indeed made the mice more susceptible to the EHV-1 infection.

The study’s findings provided insightful details regarding the implications of cross-species gene expression and its potential effects on the susceptibility to infections.

Cite This Article

APA
Minato E, Aoshima K, Kobayashi A, Ohnishi N, Sasaki N, Kimura T. (2019). Exogenous Expression of Equine MHC Class I Molecules in Mice Increases Susceptibility to Equine Herpesvirus 1 Pulmonary Infection. Vet Pathol, 56(5), 703-710. https://doi.org/10.1177/0300985819834616

Publication

ISSN: 1544-2217
NlmUniqueID: 0312020
Country: United States
Language: English
Volume: 56
Issue: 5
Pages: 703-710

Researcher Affiliations

Minato, Erina
  • 1 Laboratory of Comparative Pathology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Aoshima, Keisuke
  • 1 Laboratory of Comparative Pathology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Kobayashi, Atsushi
  • 1 Laboratory of Comparative Pathology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Ohnishi, Naomi
  • 2 Project for Personalized Cancer medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Sasaki, Nobuya
  • 3 Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Towada, Japan.
Kimura, Takashi
  • 1 Laboratory of Comparative Pathology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

MeSH Terms

  • Animals
  • Herpesviridae Infections / immunology
  • Herpesvirus 1, Equid
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Horses
  • Lung Diseases / immunology
  • Lung Diseases / virology
  • Mice
  • Mice, Transgenic

Citations

This article has been cited 1 times.
  1. Wei W, Zhang N, Chang S. Clinical study on the early systemic nursing care intervention in patients with severe pulmonary infection. Am J Transl Res 2021;13(4):3745-3751.
    pubmed: 34017560