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.
|Journal||Journal of Virology|
|State||Published - Jul 1 2017|
Bibliographical noteFunding Information:
This work was supported by Agriculture and Food Research Initiative competitive grant number 2013-68004-20360 from the USDA National Institute of Food and Agriculture (USDA-NIFA) and the Hildegard Rosa Shapiro Endowed Equine Research Fund at the Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky. We declare that we have no conflicts of interest. We gratefully acknowledge Scot Marsh of Leica Microsystems, James Begley, Bruce Maley, Cindy Meier, and Cynthia Long of the UK Imaging Facility, Kirsten Scoggin of the Maxwell H. Gluck Equine Research Center for technical support, Peter F. Moore (Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA) for advice on macrophage markers and kindly providing the anti-CD18 monoclonal antibody used in this study, William C. Davis (Monoclonal Antibody Center, College of Veterinary Medicine, Washington State University, Pullman, WA) for kindly providing anti-CD2,-CD5, and-CD172a monoclonal antibodies, Lynn Ennis, Kevin Gallagher, and Felicia Kost of the Gluck Equine Research Center Animal Resources, Diane Furry for assistance in figure preparation, and Kathleen M. Shuck for proofreading the manuscript. We also thank Lakshman Chelvarajan, Sanjay Sarkar, Ashish Tiwari, Yanqiu Li, Pamela Henney, Ashley Skillman, and Casey Edwards for the assistance provided during sample collection.
© 2017 American Society for Microbiology.
- Cellular tropism
- Equine arteritis virus
- Equine viral arteritis
- Immune response
- Male reproductive tract
- Persistent infection
ASJC Scopus subject areas
- Insect Science