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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ABSTRACT:
ORGANISM(S): Equus caballus
PROVIDER: GSE108180 | GEO | 2018/02/12
REPOSITORIES: GEO
Similar Datasets
Project description: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
| PRJNA422762 | ENA
Project description:UnlabelledPrevious studies in our laboratory have identified equine CXCL16 (EqCXCL16) to be a candidate molecule and possible cell entry receptor for equine arteritis virus (EAV). In horses, the CXCL16 gene is located on equine chromosome 11 (ECA11) and encodes a glycosylated, type I transmembrane protein with 247 amino acids. Stable transfection of HEK-293T cells with plasmid DNA carrying EqCXCL16 (HEK-EqCXCL16 cells) increased the proportion of the cell population permissive to EAV infection from <3% to almost 100%. The increase in permissiveness was blocked either by transfection of HEK-EqCXCL16 cells with small interfering RNAs (siRNAs) directed against EqCXCL16 or by pretreatment with guinea pig polyclonal antibody against EqCXCL16 protein (Gp anti-EqCXCL16 pAb). Furthermore, using a virus overlay protein-binding assay (VOPBA) in combination with far-Western blotting, gradient-purified EAV particles were shown to bind directly to the EqCXCL16 protein in vitro. The binding of biotinylated virulent EAV strain Bucyrus at 4°C was significantly higher in HEK-EqCXCL16 cells than nontransfected HEK-293T cells. Finally, the results demonstrated that EAV preferentially infects subpopulations of horse CD14(+) monocytes expressing EqCXCL16 and that infection of these cells is significantly reduced by pretreatment with Gp anti-EqCXCL16 pAb. The collective data from this study provide confirmatory evidence that the transmembrane form of EqCXCL16 likely plays a major role in EAV host cell entry processes, possibly acting as a primary receptor molecule for this virus.ImportanceOutbreaks of EVA can be a source of significant economic loss for the equine industry from high rates of abortion in pregnant mares, death in young foals, establishment of the carrier state in stallions, and trade restrictions imposed by various countries. Similar to other arteriviruses, EAV primarily targets cells of the monocyte/macrophage lineage, which, when infected, are believed to play a critical role in EVA pathogenesis. To this point, however, the host-specified molecules involved in EAV binding and entry into monocytes/macrophages have not been identified. Identification of the cellular receptors for EAV may provide insights to design antivirals and better prophylactic reagents. In this study, we have demonstrated that EqCXCL16 acts as an EAV entry receptor in EAV-susceptible cells, equine monocytes. These findings represent a significant advance in our understanding of the fundamental mechanisms associated with the entry of EAV into susceptible cells.
| S-EPMC4794689 | biostudies-literature
Project description:Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive tract, a putative target of eca-mir-128. The findings presented here suggest that SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the reproductive tract of persistently infected stallions, a chemokine axis strongly implicated in EAV persistence. This is a novel finding and warrants further investigation to identify its specific mechanism in modulating the CXCL16/CXCR6 axis in the reproductive tract of the EAV long-term carrier stallion.IMPORTANCE Equine arteritis virus (EAV) has the ability to establish long-term persistent infection in the stallion reproductive tract and to be shed in semen, which jeopardizes its worldwide control. Currently, the molecular mechanisms of viral persistence are being unraveled, and these are essential for the development of effective therapeutics to eliminate persistent infection. Recently, it has been determined that long-term persistence is associated with a specific allele of the CXCL16 gene (CXCL16S) and is maintained despite induction of local inflammatory, humoral, and mucosal antibody responses. This study demonstrated that long-term persistence is associated with the downregulation of seminal exosome miRNA eca-mir-128 and enhanced expression of its putative target, CXCL16, in the reproductive tract. For the first time, this study suggests complex interactions between eca-mir-128 and cellular elements at the site of EAV persistence and implicates this miRNA in the regulation of the CXCL16/CXCR6 axis in the reproductive tract during long-term persistence.
| S-EPMC5899189 | biostudies-literature
Project description:Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes. 80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies.
2016-04-22 | GSE64486 | GEO
Project description:Purpose: Seminal fluid (SF) is considered as a regulator on environment establishing in female reproductive tract of various mammal species without mechanism elucidated completely. This study aimed to identified the function of exosome isolated from SF on porcine endometrium. Methods: Total RNA profiles of porcine endometrial epithelial cells with seminal exosomes treatment (EXO.) or not (CTRL.) were generated by deep sequencing, in triplicate, using HiSeq 2500. Trimmed sequences were analyzed on the basis of the TopHat/Cufflinks pipeline based on the porcine genome and reference annotations obtained from Ensembl genome browser (https://www.ensembl.org). Results: 10916 transcripts, from which 70 genes were up-regulated and 114 genes were down-regulated with q-values less than 0.05 in EECs with seminal exosome treatment compared to those without exosome treatment. Conclusions: Through the gene ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis which revealed significantly enriched or decreased molecular functions, Our work demonstrated that exosomes derived from porcine seminal fluid induced endometrial immune and inflammatory response via CCL20 and AMCFII regulation specifically, which may facilitate sperm cells survival and activation, and resulting in appropriate environment required for fertilization and even implantation.
2017-10-26 | GSE106173 | GEO
Project description:Transcriptional profiling of adult mouse liver tissue comparing offspring derived from sperm and seminal plasma of normal protein diet fed males (controls, NN), sperm and seminal plasma from males fed a low protein diet fed males (LL), sperm from normal protein fed males and seminal plasma from low protein fed males (NL) or sperm from low protein diet fed males and seminal plasma from normal protein diet males (NL). The first letter denotes the diet of the sperm donor and the second letter the diet of the seminal plasma donor. Three-condition experiment: NN vs. LL, NN vs. NL, NN vs. LN. Adult offspring liver tissue. Biological replicates: 7 control (NN), 9 LL, 7 NL and 7 LN. One replicate per array chip.
2022-09-20 | GSE211520 | GEO
Project description:Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory and reproductive disease of equids. There has been significant recent progress in understanding the molecular biology of EAV and the pathogenesis of its infection in horses. In particular, the use of contemporary genomic techniques, along with the development and reverse genetic manipulation of infectious cDNA clones of several strains of EAV, has generated significant novel information regarding the basic molecular biology of the virus. Therefore, the objective of this review is to summarize current understanding of EAV virion architecture, replication, evolution, molecular epidemiology and genetic variation, pathogenesis including the influence of host genetics on disease susceptibility, host immune response, and potential vaccination and treatment strategies.
| S-EPMC7126873 | biostudies-literature
Project description:Equine lameller tissues were collected to compare normal vs laminitis generated differences in transcriptom level. Keywords: Laminitis, Equine, Diseased foot
2008-03-22 | GSE7360 | GEO
Project description:Stress fractures are microcracks in bone caused by repetitive loading and these microcracks can increase the risk of developing catastrophic fractures. Early detection of stress fractures can be difficult due to the necessity of accurate clinical detection. MicroRNAs could be used as potential diagnostic and prognostic biomarkers due to their size, abundance, tissue specificity and stability in body fluids. Global profiling of circulating plasma small RNA-sequencing between lame horses (stress fractures and non-stress fractures) and non-lame control horses and the effects and role of selected stress fracture-related miRNAs on equine bone marrow derived mesenchymal stem cells (BMMSCs) were investigated. The miRNA profiles of stress fracture cases and non-lame stress fracture cases were similar. No miRNA was identified for potential usage as a biomarker for differentiating stress fracture from lame cases. However, the miRNA profiles of lame cases and non-lame control horses were significantly different. RNA-sequencing showed three miRNAs (eca-miR-486-5p, eca-miR-26a and eca-miR-23a) were most significantly differentially expressed (p value <0.05) between lame cases and non-lame controls, which was validated by qPCR. Of these, eca-miR-486-5p demonstrated the most abundant and significant increased miRNA in the lame cases compared to non-lame control cases. Cell transfection experiments using the miR-486-5p mimic treatment in equine BMMSCs showed upregulation of the osteogenic transcription factor, Runt-related transcription factor 2 (RUNX2) and insulin-like growth factor type 1 (IGF1). A significant decrease of miR-133a in the miR-486-5p mimic treated cells was also demonstrated. Since RUNX2 is the known target of miR-133a, miR 486-5p together with miR-133a would suggest the biological importance of bone turnover and osteogenesis in equine BMMSCs, but further investigation of role of miR-486-5p and miR-133a in equine bone biology is warranted.
2024-05-23 | GSE268059 | GEO
Project description:The human seminal plasma is a potential source of biomarkers for male reproductive disorders. A tissue-profiling analysis of the main organs participating in the secretion of this body fluid was conducted to identify tissue-specific genes along the male reproductive tract. Total RNA from non pathological Human seminal vesicles were extracted and hybridized on Affymetrix microarrays. Expression signals in seminal vesicles (present dataset), prostates (GEO; GSE7307), epidydimises (GEO; GSE7808) and testicular samples (Arrayexpress; E-TABM-130) were compared to identify genes that are detected in one of these organs only.
2010-06-08 | E-GEOD-17340 | biostudies-arrayexpress