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Journal of virology2017; 91(13); doi: 10.1128/JVI.00418-17

Equine Arteritis Virus Has Specific Tropism for Stromal Cells and CD8+ T and CD21+ B Lymphocytes but Not for Glandular Epithelium at the Primary Site of Persistent Infection in the Stallion Reproductive Tract.

Abstract: Equine arteritis virus (EAV) has a global impact on the equine industry as the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. A distinctive feature of EAV infection is that it establishes long-term persistent infection in 10 to 70% of infected stallions (carriers). In these stallions, EAV is detectable only in the reproductive tract, and viral persistence occurs despite the presence of high serum neutralizing antibody titers. Carrier stallions constitute the natural reservoir of the virus as they continuously shed EAV in their semen. Although the accessory sex glands have been implicated as the primary sites of EAV persistence, the viral host cell tropism and whether viral replication in carrier stallions occurs in the presence or absence of host inflammatory responses remain unknown. In this study, dual immunohistochemical and immunofluorescence techniques were employed to unequivocally demonstrate that the ampulla is the main EAV tissue reservoir rather than immunologically privileged tissues (i.e., testes). Furthermore, we demonstrate that EAV has specific tropism for stromal cells (fibrocytes and possibly tissue macrophages) and CD8+ T and CD21+ B lymphocytes but not glandular epithelium. Persistent EAV infection is associated with moderate, multifocal lymphoplasmacytic ampullitis comprising clusters of B (CD21+) lymphocytes and significant infiltration of T (CD3+, CD4+, CD8+, and CD25+) lymphocytes, tissue macrophages, and dendritic cells (Iba-1+ and CD83+), with a small number of tissue macrophages expressing CD163 and CD204 scavenger receptors. This study suggests that EAV employs complex immune evasion mechanisms that warrant further investigation.IMPORTANCE The major challenge for the worldwide control of EAV is that this virus has the distinctive ability to establish persistent infection in the stallion's reproductive tract as a mechanism to ensure its maintenance in equid populations. Therefore, the precise identification of tissue and cellular tropism of EAV is critical for understanding the molecular basis of viral persistence and for development of improved prophylactic or treatment strategies. This study significantly enhances our understanding of the EAV carrier state in stallions by unequivocally identifying the ampullae as the primary sites of viral persistence, combined with the fact that persistence involves continuous viral replication in fibrocytes (possibly including tissue macrophages) and T and B lymphocytes in the presence of detectable inflammatory responses, suggesting the involvement of complex viral mechanisms of immune evasion. Therefore, EAV persistence provides a powerful new natural animal model to study RNA virus persistence in the male reproductive tract.
Copyright © 2017 American Society for Microbiology.
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Publication Date: 2017-06-09 PubMed ID: 28424285PubMed Central: PMC5469258DOI: 10.1128/JVI.00418-17Google Scholar: Lookup
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  • Journal Article

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 study discusses how the Equine Arteritis Virus (EAV) uniquely affects specific cells within a stallion’s reproductive tract, establishing persistent infection despite the immune response. It provides critical insight into understanding the EAV’s carrier state in stallions and offers a natural animal model for studying RNA virus persistence in the male reproductive tract.

Research Context

  • This research is based on Equine Arteritis Virus (EAV), a globally recognized disease that affects horses. EAV is the cause of equine viral arteritis (EVA), a disease with respiratory, systemic, and reproductive impacts.
  • EAV manages to establish persistent infections in 10 to 70% of infected stallions, despite existing neutralizing antibody responses in the horses. This ability to persist makes the ‘carrier’ stallions the natural virus reservoir, as they continually shed the virus in their semen.
  • However, the focus of EAV persistence, as well as the specifics of its interaction with different cell types (its “tropism”), was previously unknown, driving the need for this research.

Findings and Implications

  • The researchers used advanced techniques to confirm that the main tissue reservoir of EAV is the ampulla within the stallion’s reproductive tract, rather than the testes which were previously suggested as possible sites.
  • The study found that EAV specifically targets stromal cells (like fibrocytes and possibly tissue macrophages) and two types of lymphocytes (CD8 T and CD21 B cells), but it leaves the glandular epithelium unaffected. This specific targeting is referred to as the virus’s ‘tropism’.
  • Persistent EAV infection was associated with observable inflammation symptoms, defined as ‘ampullitis’, which involved the aggregation of the targeted lymphocytes and infiltration of other immune cells. This could suggest a complex interplay between the virus and the host’s immune response.
  • Understanding EAV’s cellular tropism, persistence mechanisms, and immune system interactions can contribute to better prevention or treatment strategies against EVA.
  • The results also open up a new natural animal model to study RNA virus persistence in the male reproductive tract, which could be of significant use in other virology studies.

Cite This Article

APA
Carossino M, Loynachan AT, Canisso IF, Cook RF, Campos JR, Nam B, Go YY, Squires EL, Troedsson MHT, Swerczek T, Del Piero F, Bailey E, Timoney PJ, Balasuriya UBR. (2017). Equine Arteritis Virus Has Specific Tropism for Stromal Cells and CD8+ T and CD21+ B Lymphocytes but Not for Glandular Epithelium at the Primary Site of Persistent Infection in the Stallion Reproductive Tract. J Virol, 91(13). https://doi.org/10.1128/JVI.00418-17

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 91
Issue: 13

Researcher Affiliations

Carossino, Mariano
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Loynachan, Alan T
  • University of Kentucky Veterinary Diagnostic Laboratory, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Canisso, Igor F
  • Department of Veterinary Clinical Medicine and Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
Cook, R Frank
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Campos, Juliana R
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Nam, Bora
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Go, Yun Young
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
  • Virus Research and Testing Group, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon, South Korea.
Squires, Edward L
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Troedsson, Mats H T
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Swerczek, Thomas
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Del Piero, Fabio
  • Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Bailey, Ernest
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Timoney, Peter J
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Balasuriya, Udeni B R
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA ubalasuriya@uky.edu.

MeSH Terms

  • Animals
  • Arterivirus Infections / veterinary
  • Arterivirus Infections / virology
  • B-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / virology
  • Epithelium / virology
  • Equartevirus / physiology
  • Fluorescent Antibody Technique
  • Genitalia / virology
  • Horse Diseases / virology
  • Horses
  • Immunohistochemistry
  • Male
  • Stromal Cells / virology
  • Viral Tropism

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Citations

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