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Home / Equine Research Bank / PLoS Pathog / Equine arteritis virus long-term persistence is orchestrated...
PLoS pathogens2019; 15(7); e1007950; doi: 10.1371/journal.ppat.1007950

Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis.

Abstract: Equine arteritis virus (EAV) has the unique ability to establish long-term persistent infection in the reproductive tract of stallions and be sexually transmitted. Previous studies showed that long-term persistent infection is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistence is maintained despite the presence of local inflammatory and humoral and mucosal antibody responses. Here, we performed transcriptomic analysis of the ampullae, the primary site of EAV persistence in long-term EAV carrier stallions, to understand the molecular signatures of viral persistence. We demonstrated that the local CD8+ T lymphocyte response is predominantly orchestrated by the transcription factors eomesodermin (EOMES) and nuclear factor of activated T-cells cytoplasmic 2 (NFATC2), which is likely modulated by the upregulation of inhibitory receptors. Most importantly, EAV persistence is associated with an enhanced expression of CXCL16 and CXCR6 by infiltrating lymphocytes, providing evidence of the implication of this chemokine axis in the pathogenesis of persistent EAV infection in the stallion reproductive tract. Furthermore, we have established a link between the CXCL16 genotype and the gene expression profile in the ampullae of the stallion reproductive tract. Specifically, CXCL16 acts as a "hub" gene likely driving a specific transcriptional network. The findings herein are novel and strongly suggest that RNA viruses such as EAV could exploit the CXCL16/CXCR6 axis in order to modulate local inflammatory and immune responses in the male reproductive tract by inducing a dysfunctional CD8+ T lymphocyte response and unique lymphocyte homing in the reproductive tract.
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Publication Date: 2019-07-29 PubMed ID: 31356622PubMed Central: PMC6692045DOI: 10.1371/journal.ppat.1007950Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

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.

This study examines the unique ability of Equine arteritis virus (EAV) to maintain persistent infections in the reproductive tract of stallions and reveals a complex interplay of immune responses and virus survival strategies, highlighting the role of the CXCL16/CXCR6 axis.

Understanding EAV Infections

  • The focus of the study is the Equine arteritis virus (EAV), which can establish a long-standing persistent infection within the reproductive tract of stallions, leading to sexual transmission.
  • EAV’s long-term persistence is believed to be related to an allele (variation) of the CXCL16 gene (specifically the CXCL16S allele).
  • EAV can continue to thrive even when there are manifested local inflammatory responses and the active involvement of humoral and mucosal antibodies.

A Detailed Look at EAV Persistence

  • To explore how EAV continues to persist, the researchers conducted a transcriptomic analysis of the ampullae, which is the primary location of EAV persistence in carrier stallions.
  • The analysis focused on understanding the identifying molecular markers associated with the long-term presence of the virus.
  • The findings suggest that the local CD8+ T lymphocyte response, significant in the immune defense against viruses, is regulated primarily by the transcription factors eomesodermin (EOMES) and nuclear factor of activated T-cells cytoplasmic 2 (NFATC2).
  • The study also indicates that the upregulated expression of inhibitory receptors tempers these T-cell responses.

Role of the CXCL16/CXCR6 Axis

  • The central discovery of the study is the association of EAV persistence with an increased display of CXCL16 and CXCR6 by infiltrating lymphocytes in the reproductive tract.
  • This association provides strong evidence implicating this chemokine axis (CXCL16/CXCR6) in the continuation of EAV infections within the reproductive tract of stallions.
  • The researchers believe that EAV exploits this axis to modulate local inflammatory and immune responses by promoting a deficient response from CD8+ T lymphocytes and enabling specific lymphocyte homing in the reproductive tract.
  • The genotype of CXCL16 also influences the gene expression pattern within the stallion reproductive tract; specifically, CXCL16 acts as a core or “hub” gene that may direct a particular transcriptional network.

Implications of the Findings

  • The study provides novel insights into our understanding of long-term viral persistence, specifically within the unique context of stallion reproductive physiology and EAV.
  • These findings could enhance our comprehension of how RNA viruses such as EAV evolve strategies to subvert host defenses and ensure their survival and propagation.

Cite This Article

APA
Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Cook RF, Timoney PJ, Balasuriya UBR. (2019). Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis. PLoS Pathog, 15(7), e1007950. https://doi.org/10.1371/journal.ppat.1007950

Publication

PLoS pathogens
ISSN: 1553-7374
NlmUniqueID: 101238921
Country: United States
Language: English
Volume: 15
Issue: 7
Pages: e1007950

Researcher Affiliations

Carossino, Mariano
  • Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States of America.
Dini, Pouya
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
  • Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Kalbfleisch, Theodore S
  • Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, KY, United States of America.
Loynachan, Alan T
  • University of Kentucky Veterinary Diagnostic Laboratory, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Canisso, Igor F
  • Department of Veterinary Clinical Medicine, and Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL, United States of America.
Cook, R Frank
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Timoney, Peter J
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Balasuriya, Udeni B R
  • Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States of America.

MeSH Terms

  • Animals
  • Arterivirus Infections / genetics
  • Arterivirus Infections / immunology
  • Arterivirus Infections / veterinary
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Carrier State / immunology
  • Carrier State / veterinary
  • Carrier State / virology
  • Chemokine CXCL16 / genetics
  • Chemokine CXCL16 / immunology
  • Equartevirus / immunology
  • Equartevirus / pathogenicity
  • Gene Expression Profiling
  • Genitalia, Male / immunology
  • Genitalia, Male / pathology
  • Genitalia, Male / virology
  • Horse Diseases / genetics
  • Horse Diseases / immunology
  • Horse Diseases / virology
  • Horses
  • Host Microbial Interactions / genetics
  • Host Microbial Interactions / immunology
  • Male
  • Receptors, CXCR6 / genetics
  • Receptors, CXCR6 / immunology
  • Receptors, Virus / immunology
  • Transcription Factors / immunology
  • Virus Shedding / genetics
  • Virus Shedding / immunology

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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