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

Carossino, Mariano ; Dini, Pouya ; Kalbfleisch, Theodore S ; Loynachan, Alan T ; Canisso, Igor F ; Cook, R Frank ; Timoney, Peter J ; Balasuriya, Udeni B R Osterrieder, Nikolaus

PLoS pathogens, 2019-07, Vol.15 (7), p.e1007950-e1007950 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis
Autor: Carossino, Mariano ; Dini, Pouya ; Kalbfleisch, Theodore S ; Loynachan, Alan T ; Canisso, Igor F ; Cook, R Frank ; Timoney, Peter J ; Balasuriya, Udeni B R
Osterrieder, Nikolaus
Assuntos: Abortion ; Animal diseases ; Animals ; Antibodies ; Arterivirus Infections - genetics ; Arterivirus Infections - immunology ; Arterivirus Infections - veterinary ; Bioinformatics ; Biology and Life Sciences ; Carrier State - immunology ; Carrier State - veterinary ; Carrier State - virology ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - virology ; Cell migration ; Chemokine CXCL16 - genetics ; Chemokine CXCL16 - immunology ; Chemokines ; CXCL16 protein ; Edema ; Equartevirus - immunology ; Equartevirus - pathogenicity ; Gene expression ; Gene Expression Profiling ; Genitalia, Male - immunology ; Genitalia, Male - pathology ; Genitalia, Male - virology ; Genomes ; Genotypes ; Homing ; Horse Diseases - genetics ; Horse Diseases - immunology ; Horse Diseases - virology ; Horses ; Host Microbial Interactions - genetics ; Host Microbial Interactions - immunology ; Immune response ; Infections ; Inflammation ; Laboratories ; Lymphocytes ; Male ; Medicine and Health Sciences ; MicroRNAs ; Mucosa ; Pathogenesis ; Persistent infection ; Receptors ; Receptors, CXCR6 - genetics ; Receptors, CXCR6 - immunology ; Receptors, Virus - immunology ; Reproductive system ; RNA viruses ; Software ; Transcription factors ; Transcription Factors - immunology ; Transplants & implants ; Veterinary colleges ; Veterinary medicine ; Virus Shedding - genetics ; Virus Shedding - immunology ; Viruses
É parte de: PLoS pathogens, 2019-07, Vol.15 (7), p.e1007950-e1007950
Notas: new_version
ObjectType-Article-1
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Current address: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America
The authors have declared that no competing interests exist.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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

Carossino, Mariano ; Dini, Pouya ; Kalbfleisch, Theodore S ; Loynachan, Alan T ; Canisso, Igor F ; Cook, R Frank ; Timoney, Peter J ; Balasuriya, Udeni B R Osterrieder, Nikolaus

United States: Public Library of Science

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