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Long-term persistent infection with equine arteritis virus is associated with the upregulation of specific CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis in the ampullae of the stallion reproductive tract

ABSTRACT: Long-term persistent infection with equine arteritis virus is associated with the upregulation of specific CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis in the ampullae of the stallion reproductive tract

PROVIDER: PRJNA473438 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7226620_1.fastq.gz	Fastqsanger.gz
	SRR7226620_2.fastq.gz	Fastqsanger.gz
	SRR7226611_1.fastq.gz	Fastqsanger.gz
	SRR7226611_2.fastq.gz	Fastqsanger.gz
	SRR7226621_1.fastq.gz	Fastqsanger.gz

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Long-term persistent infection with equine arteritis virus is associated with the upregulation of specific CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis in the ampullae of the stallion reproductive tract

Project description:We performed whole transcriptome analysis of the ampullae, the primary site of EAV persistence, derived from long-term carrier stallions to understand the molecular signature of persistent infection. We demonstrated that long-term persistence is characterized by a local CD8+ T lymphocyte response predominantly driven by the transcription factors EOMES and NFATC2.We showed that EAV persistence is associated with an enhanced expression of CXCL16/CXCR6 in infiltrating lymphocytes. Furthermore, we established a link between the CXCL16 genotype and the gene expression profile at the site of persistence following EAV infection. Co-expression network analysis identified CXCL16 as a “hub” gene, likely driving a specific transcriptional network.

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Downregulation of eca-mir-128 in seminal exosomes and enhanced expression of CXCL16 in the stallion reproductive tract are associated with equine arteritis virus long-term persistent infection

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Project description: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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