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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

(2019) PLOS PATHOGENS. 15(7).
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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.
Keywords
Immunology, Genetics, Molecular Biology, Microbiology, Parasitology, Virology, INFECTIOUS CDNA-CLONE, CELL EXHAUSTION, CARRIER STATE, GENE, STRAIN, PROTEINS, PATHWAYS, SPREAD, CXCR6, NFAT

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MLA
Carossino, Mariano, et al. “Equine Arteritis Virus Long-Term Persistence Is Orchestrated by CD8+ T Lymphocyte Transcription Factors, Inhibitory Receptors, and the CXCL16/CXCR6 Axis.” PLOS PATHOGENS, edited by Nikolaus Osterrieder, vol. 15, no. 7, 2019, doi:10.1371/journal.ppat.1007950.
APA
Carossino, M., Dini, P., Kalbfleisch, T. S., Loynachan, A. T., Canisso, I. F., Cook, R. F., … Balasuriya, U. B. R. (2019). Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis. PLOS PATHOGENS, 15(7). https://doi.org/10.1371/journal.ppat.1007950
Chicago author-date
Carossino, Mariano, Pouya Dini, Theodore S. Kalbfleisch, Alan T. Loynachan, Igor F. Canisso, R. Frank Cook, Peter J. Timoney, and Udeni B. R. Balasuriya. 2019. “Equine Arteritis Virus Long-Term Persistence Is Orchestrated by CD8+ T Lymphocyte Transcription Factors, Inhibitory Receptors, and the CXCL16/CXCR6 Axis.” Edited by Nikolaus Osterrieder. PLOS PATHOGENS 15 (7). https://doi.org/10.1371/journal.ppat.1007950.
Chicago author-date (all authors)
Carossino, Mariano, Pouya Dini, Theodore S. Kalbfleisch, Alan T. Loynachan, Igor F. Canisso, R. Frank Cook, Peter J. Timoney, and Udeni B. R. Balasuriya. 2019. “Equine Arteritis Virus Long-Term Persistence Is Orchestrated by CD8+ T Lymphocyte Transcription Factors, Inhibitory Receptors, and the CXCL16/CXCR6 Axis.” Ed by. Nikolaus Osterrieder. PLOS PATHOGENS 15 (7). doi:10.1371/journal.ppat.1007950.
Vancouver
1.
Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Cook RF, et al. Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis. Osterrieder N, editor. PLOS PATHOGENS. 2019;15(7).
IEEE
[1]
M. Carossino et al., “Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis,” PLOS PATHOGENS, vol. 15, no. 7, 2019.
@article{8659014,
  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.}},
  articleno    = {{e1007950}},
  author       = {{Carossino, Mariano and Dini, Pouya and Kalbfleisch, Theodore S. and Loynachan, Alan T. and Canisso, Igor F. and Cook, R. Frank and Timoney, Peter J. and Balasuriya, Udeni B. R.}},
  editor       = {{Osterrieder, Nikolaus}},
  issn         = {{1553-7366}},
  journal      = {{PLOS PATHOGENS}},
  keywords     = {{Immunology,Genetics,Molecular Biology,Microbiology,Parasitology,Virology,INFECTIOUS CDNA-CLONE,CELL EXHAUSTION,CARRIER STATE,GENE,STRAIN,PROTEINS,PATHWAYS,SPREAD,CXCR6,NFAT}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{42}},
  title        = {{Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis}},
  url          = {{http://dx.doi.org/10.1371/journal.ppat.1007950}},
  volume       = {{15}},
  year         = {{2019}},
}

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