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1.
Commun Biol ; 6(1): 963, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735603

RESUMO

Centromeres are epigenetically specified by the histone H3 variant CENP-A. Although mammalian centromeres are typically associated with satellite DNA, we previously demonstrated that the centromere of horse chromosome 11 (ECA11) is completely devoid of satellite DNA. We also showed that the localization of its CENP-A binding domain is not fixed but slides within an about 500 kb region in different individuals, giving rise to positional alleles. These epialleles are inherited as Mendelian traits but their position can move in one generation. It is still unknown whether centromere sliding occurs during meiosis or during development. Here, we first improve the sequence of the ECA11 centromeric region in the EquCab3.0 assembly. Then, to test whether centromere sliding may occur during development, we map the CENP-A binding domains of ECA11 using ChIP-seq in five tissues of different embryonic origin from the four horses of the equine FAANG (Functional Annotation of ANimal Genomes) consortium. Our results demonstrate that the centromere is localized in the same region in all tissues, suggesting that the position of the centromeric domain is maintained during development.


Assuntos
Centrômero , DNA Satélite , Humanos , Animais , Cavalos , Proteína Centromérica A/genética , Centrômero/genética , Histonas , Meiose , Mamíferos
2.
Trends Genet ; 39(11): 808-809, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37423869

RESUMO

Native Americans of the Plains and Rocky Mountains are renowned for their horsemanship. Taylor et al. recently used ancient DNA and other bioarcheological approaches to document how horses dispersed throughout America and transformed Native American societies following their introduction by the Spanish in 1519, well before the arrival of European settlers.


Assuntos
Indígena Americano ou Nativo do Alasca , DNA Antigo , Cavalos , Animais , Humanos , DNA Mitocondrial/genética , Cavalos/genética
3.
Front Genet ; 13: 871875, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495124

RESUMO

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. Following natural infection, up to 70% of the infected stallions can remain persistently infected over 1 year (long-term persistent infection [LTPI]) and shed EAV in their semen. Thus, the LTP-infected stallions play a pivotal role in maintaining and perpetuating EAV in the equine population. Previous studies identified equine C-X-C motif chemokine ligand 16 (CXCL16) as a critical host cell factor determining LTPI in the stallion's reproductive tract. Two alleles (CXCL16 S and CXCL16 r ) were identified in the equine population and correlated with the susceptibility or resistance of a CD3+ T cell subpopulation in peripheral blood to in vitro EAV infection, respectively. Interestingly, CXCL16 S has been linked to the establishment of LTPI in stallions, and thus, genotyping stallions based on CXCL16 S/r would allow identification of those at the highest risk of establishing LTPI. Thus, we developed a TaqMan® allelic discrimination qPCR assay for the genotyping of the equine CXCL16 gene based on the identification of a single nucleotide polymorphism in position 1,073 based on NCBI gene ID: 100061442 (or position 527 based on Ensembl: ENSECAG00000018406.2) located in exon 2. One hundred and sixty horses from four breeds were screened for the CD3+ T cell susceptibility phenotype to EAV infection by flow cytometry and subsequently sequenced to determine CXCL16 allelic composition. Genotyping by Sanger sequencing determined that all horses with the resistant CD3+ T cell phenotype were homozygous for CXCL16 r while horses with the susceptible CD3+ T cell phenotype carried at least one CXCL16 S allele or homozygous for CXCL16 S . In addition, genotypification with the TaqMan® allelic discrimination qPCR assay showed perfect agreement with Sanger sequencing and flow cytometric analysis. In conclusion, the new TaqMan® allelic discrimination genotyping qPCR assay can be used to screen prepubertal colts for the presence of the CXCL16 genotype. It is highly recommended that colts that carry the susceptible genotype (CXCL16  S/S or CXCL16 S/r ) are vaccinated against EAV after 6 months of age to prevent the establishment of LTPI carriers following possible natural infection with EAV.

4.
Annu Rev Anim Biosci ; 10: 131-150, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780248

RESUMO

Thoroughbred horses have been selected for racing performance for more than 400 years. Despite continued selection, race times have not improved significantly during the past 60 years, raising the question of whether genetic variation for racing performance still exists. Studies using phenotypes such as race time, money earned, and handicapping, however, demonstrate that there is extensive variation within these traits and that they are heritable. Even so, these are poor measures of racing success since Thoroughbreds race at different ages and distances and on different types of tracks, and some may not race at all. With the advent of genomic tools, DNA variants are being identified that contribute to racing success. Aside from strong associations for myostatin variants with best racing distance, weak to modest associations with racing phenotypes are reported for other genomic regions. These data suggest that diverse genetic strategies have contributed to producing a successful racehorse, and genetic variation contributing to athleticism remains important.


Assuntos
Esportes , Animais , Genoma , Cavalos/genética , Fenótipo
5.
Proc Natl Acad Sci U S A ; 118(16)2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33853939

RESUMO

Most autosomal genes in the placenta show a biallelic expression pattern. However, some genes exhibit allele-specific transcription depending on the parental origin of the chromosomes on which the copy of the gene resides. Parentally expressed genes are involved in the reciprocal interaction between maternal and paternal genes, coordinating the allocation of resources between fetus and mother. One of the main challenges of studying parental-specific allelic expression (allele-specific expression [ASE]) in the placenta is the maternal cellular remnant at the fetomaternal interface. Horses (Equus caballus) have an epitheliochorial placenta in which both the endometrial epithelium and the epithelium of the chorionic villi are juxtaposed with minimal extension into the uterine mucosa, yet there is no information available on the allelic gene expression of equine chorioallantois (CA). In the current study, we present a dataset of 1,336 genes showing ASE in the equine CA (https://pouya-dini.github.io/equine-gene-db/) along with a workflow for analyzing ASE genes. We further identified 254 potentially imprinted genes among the parentally expressed genes in the equine CA and evaluated the expression pattern of these genes throughout gestation. Our gene ontology analysis implies that maternally expressed genes tend to decrease the length of gestation, while paternally expressed genes extend the length of gestation. This study provides fundamental information regarding parental gene expression during equine pregnancy, a species with a negligible amount of maternal cellular remnant in its placenta. This information will provide the basis for a better understanding of the role of parental gene expression in the placenta during gestation.


Assuntos
Impressão Genômica/genética , Cavalos/genética , Placentação/genética , Alelos , Animais , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Impressão Genômica/fisiologia , Cavalos/metabolismo , Placenta/metabolismo , Gravidez
6.
PLoS One ; 16(2): e0247123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33592064

RESUMO

The present research aimed to characterize the Persian Kurdish horse population relative to the Persian Arabian and American Thoroughbred populations using genome-wide SNP data. Fifty-eight Kurdish, 38 Persian Arabian and 83 Thoroughbred horses were genotyped across 670,796 markers. After quality control and pruning to eliminate linkage disequilibrium between loci which resulted in 13,554 SNPs in 52 Kurdish, 24 Persian Arabian and 58 Thoroughbred horses, the Kurdish horses were generally distinguished from the Persian Arabian samples by Principal Component Analyses, cluster analyses and calculation of pairwise FST. Both Persian breeds were discriminated from the Thoroughbred. Pairwise FST between the two Persian samples (0.013) was significantly greater than zero and several fold less than those found between the Thoroughbred and Kurdish (0.052) or Thoroughbred and Persian Arabian (0.057). Cluster analysis assuming three genetic clusters assigned the Kurdish horse and Thoroughbred to distinct clusters (0.942 in cluster 2 and 0.953 in cluster 3 respectively); the Persian Arabian was not in a distinct cluster (0.519 in cluster 1), demonstrating shared ancestry or recent admixture with the Kurdish breed. Diversity as quantified by expected heterozygosity was the highest in the Kurdish horse (0.342), followed by the Persian Arabian (0.328) and the Thoroughbred (0.326). Analysis of Molecular Variance showed that 4.47% of the genetic variation was present among populations (P<0.001). Population-specific inbreeding indices (FIS) were not significantly different from zero in any of the populations. Analysis of individual inbreeding based on runs of homozygosity using a larger SNP set suggested greater diversity in both the Kurdish and Persian Arabian than in the Thoroughbred. These results have implications for developing conservation strategies to achieve sound breeding goals while maintaining genetic diversity.


Assuntos
Repetições de Microssatélites/genética , Animais , Análise por Conglomerados , Feminino , Variação Genética/genética , Genômica , Genótipo , Técnicas de Genotipagem , Heterozigoto , Homozigoto , Cavalos , Desequilíbrio de Ligação/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética , Análise de Componente Principal
8.
Equine Vet J ; 52(6): 794-798, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32153055

RESUMO

BACKGROUND: Equid herpesvirus (EHV-1) infections in horses can lead to equine herpesvirus myeloencephalopathy (EHM), characterised by neurological clinical signs. The sporadic occurrence of the disease in horse herds suggests a host genetic component. A recent study reported an association between the occurrence of EHM and genetic markers on horse chromosome 6 (ECA6). OBJECTIVES: To investigate the association of EHM with genetic host factors, especially with reference to the association reported for ECA6. STUDY DESIGN: Genome-wide association study (GWAS) was conducted based on 94 horses that had EHV-1 infections and comparing the 27 developing clinical EHM to the 67 which did not. METHODS: DNA samples were tested from 94 horses for 382,529 single nucleotide polymorphisms (SNPs) with the Affymetrix Axiom 670K SNP array to identify possible associations with EHM. The data analysis included tests for basic, additive, dominant and recessive modes of inheritance, haplotype associations and runs of homozygosity (ROH). RESULTS: Results from this study did not identify significant SNPs, haplotypes or ROH associations with the development of EHM following EHV-1 infections and excluded the involvement of a recessive genetic factor in the susceptibility to develop EHM. MAIN LIMITATIONS: Sample size and complex phenotype. CONCLUSIONS: The results exclude the involvement of a recessive genetic factor in the susceptibility to develop clinically apparent EHM but do not have the power to exclude the involvement of other, complex host genetic factors. Furthermore, there was no association between development of EHM and genes on equine chromosome 6, as previously reported.


Assuntos
Infecções por Herpesviridae/genética , Infecções por Herpesviridae/veterinária , Herpesvirus Equídeo 1/genética , Doenças dos Cavalos/genética , Varicellovirus , Animais , Estudo de Associação Genômica Ampla/veterinária , Cavalos
10.
Genes (Basel) ; 10(7)2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269762

RESUMO

Increasing evidence suggests that overlapping genes are much more common in eukaryotic genomes than previously thought. These different-strand overlapping genes are potential sense-antisense (SAS) pairs, which might have regulatory effects on each other. In the present study, we identified the SAS loci in the equine genome using previously generated stranded, paired-end RNA sequencing data from the equine chorioallantois. We identified a total of 1261 overlapping loci. The ratio of the number of overlapping regions to chromosomal length was numerically higher on chromosome 11 followed by chromosomes 13 and 12. These results show that overlapping transcription is distributed throughout the equine genome, but that distributions differ for each chromosome. Next, we evaluated the expression patterns of SAS pairs during the course of gestation. The sense and antisense genes showed an overall positive correlation between the sense and antisense pairs. We further provide a list of SAS pairs with both positive and negative correlation in their expression patterns throughout gestation. This study characterizes the landscape of sense and antisense gene expression in the placenta for the first time and provides a resource that will enable researchers to elucidate the mechanisms of sense/antisense regulation during pregnancy.


Assuntos
Homologia de Genes , Cavalos/genética , Placenta/metabolismo , Animais , Feminino , Loci Gênicos , Gravidez , Transcriptoma
11.
Commun Biol ; 1: 197, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30456315

RESUMO

Recent advances in genomic sequencing technology and computational assembly methods have allowed scientists to improve reference genome assemblies in terms of contiguity and composition. EquCab2, a reference genome for the domestic horse, was released in 2007. Although of equal or better quality compared to other first-generation Sanger assemblies, it had many of the shortcomings common to them. In 2014, the equine genomics research community began a project to improve the reference sequence for the horse, building upon the solid foundation of EquCab2 and incorporating new short-read data, long-read data, and proximity ligation data. Here, we present EquCab3. The count of non-N bases in the incorporated chromosomes is improved from 2.33 Gb in EquCab2 to 2.41 Gb in EquCab3. Contiguity has also been improved nearly 40-fold with a contig N50 of 4.5 Mb and scaffold contiguity enhanced to where all but one of the 32 chromosomes is comprised of a single scaffold.

12.
BMC Genomics ; 18(1): 565, 2017 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-28750625

RESUMO

BACKGROUND: To date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array. RESULTS: Using whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, and genotypes from lower-density, legacy SNP arrays, a subset of ~5 million high-quality, high-density array candidate SNPs were selected based on breed representation and uniform spacing across the genome. Considering probe design recommendations from a commercial vendor (Affymetrix, now Thermo Fisher Scientific) a set of ~2 million SNPs were selected for a next-generation high-density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array from a cohort of 332 horses from 20 breeds and a lower-density array, consisting of ~670 thousand SNPs (MNEc670k), was designed for genotype imputation. CONCLUSIONS: Here, we document the steps taken to design both the MNEc2M and MNEc670k arrays, report genomic and technical properties of these genotyping platforms, and demonstrate the imputation capabilities of these tools for the domestic horse.


Assuntos
Técnicas de Genotipagem/métodos , Cavalos/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Polimorfismo de Nucleotídeo Único , Animais , Frequência do Gene , Técnicas de Genotipagem/normas , Desequilíbrio de Ligação , Análise de Sequência com Séries de Oligonucleotídeos/normas , Padrões de Referência , Sequenciamento Completo do Genoma
13.
J Virol ; 91(13)2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28424285

RESUMO

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.IMPORTANCE The major challenge for the worldwide control of EAV is that this virus has the distinctive ability to establish persistent infection in the stallion's reproductive tract as a mechanism to ensure its maintenance in equid populations. Therefore, the precise identification of tissue and cellular tropism of EAV is critical for understanding the molecular basis of viral persistence and for development of improved prophylactic or treatment strategies. This study significantly enhances our understanding of the EAV carrier state in stallions by unequivocally identifying the ampullae as the primary sites of viral persistence, combined with the fact that persistence involves continuous viral replication in fibrocytes (possibly including tissue macrophages) and T and B lymphocytes in the presence of detectable inflammatory responses, suggesting the involvement of complex viral mechanisms of immune evasion. Therefore, EAV persistence provides a powerful new natural animal model to study RNA virus persistence in the male reproductive tract.


Assuntos
Linfócitos B/virologia , Linfócitos T CD8-Positivos/virologia , Epitélio/virologia , Equartevirus/fisiologia , Genitália/virologia , Células Estromais/virologia , Tropismo Viral , Animais , Infecções por Arterivirus/veterinária , Infecções por Arterivirus/virologia , Imunofluorescência , Doenças dos Cavalos/virologia , Cavalos , Imuno-Histoquímica , Masculino
14.
PLoS Genet ; 12(12): e1006467, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27930647

RESUMO

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10-70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001) and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and EqCXCL16Sb exert a dominant mode of inheritance. Most importantly, the protein isoform EqCXCL16S but not EqCXCL16R can function as an EAV cellular receptor. Although both molecules have equal chemoattractant potential, EqCXCL16S has significantly higher scavenger receptor and adhesion properties compared to EqCXCL16R.


Assuntos
Infecções por Arterivirus/genética , Quimiocinas CXC/genética , Equartevirus/genética , Doenças dos Cavalos/genética , Alelos , Sequência de Aminoácidos/genética , Animais , Infecções por Arterivirus/veterinária , Infecções por Arterivirus/virologia , Complexo CD3/genética , Complexo CD3/imunologia , Equartevirus/patogenicidade , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Doenças dos Cavalos/virologia , Cavalos/genética , Cavalos/virologia , Masculino , Filogenia , Sêmen/metabolismo , Linfócitos T/imunologia , Linfócitos T/patologia
15.
G3 (Bethesda) ; 6(7): 2213-23, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27207956

RESUMO

Skeletal atavism in Shetland ponies is a heritable disorder characterized by abnormal growth of the ulna and fibula that extend the carpal and tarsal joints, respectively. This causes abnormal skeletal structure and impaired movements, and affected foals are usually killed. In order to identify the causal mutation we subjected six confirmed Swedish cases and a DNA pool consisting of 21 control individuals to whole genome resequencing. We screened for polymorphisms where the cases and the control pool were fixed for opposite alleles and observed this signature for only 25 SNPs, most of which were scattered on genome assembly unassigned scaffolds. Read depth analysis at these loci revealed homozygosity or compound heterozygosity for two partially overlapping large deletions in the pseudoautosomal region (PAR) of chromosome X/Y in cases but not in the control pool. One of these deletions removes the entire coding region of the SHOX gene and both deletions remove parts of the CRLF2 gene located downstream of SHOX. The horse reference assembly of the PAR is highly fragmented, and in order to characterize this region we sequenced bacterial artificial chromosome (BAC) clones by single-molecule real-time (SMRT) sequencing technology. This considerably improved the assembly and enabled size estimations of the two deletions to 160-180 kb and 60-80 kb, respectively. Complete association between the presence of these deletions and disease status was verified in eight other affected horses. The result of the present study is consistent with previous studies in humans showing crucial importance of SHOX for normal skeletal development.


Assuntos
Osso e Ossos/metabolismo , Mapeamento Cromossômico , Genoma , Proteínas de Homeodomínio/genética , Cavalos/genética , Regiões Pseudoautossômicas/química , Deleção de Sequência , Animais , Sequência de Bases , Osso e Ossos/anormalidades , Feminino , Loci Gênicos , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/metabolismo , Homozigoto , Masculino , Regiões Pseudoautossômicas/metabolismo , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo
16.
J Virol ; 90(7): 3366-84, 2016 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-26764004

RESUMO

UNLABELLED: Previous 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. IMPORTANCE: Outbreaks 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.


Assuntos
Quimiocinas CXC/fisiologia , Equartevirus/fisiologia , Especificidade de Hospedeiro/genética , Receptores Virais/genética , Internalização do Vírus , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/imunologia , Infecções por Arterivirus/virologia , Sequência de Bases , Linhagem Celular , Quimiocinas CXC/antagonistas & inibidores , Quimiocinas CXC/genética , Cricetinae , Equartevirus/genética , Cobaias , Células HEK293 , Doenças dos Cavalos/virologia , Cavalos , Humanos , Interferência de RNA , RNA Interferente Pequeno/genética , Coelhos , Receptores Virais/metabolismo , Análise de Sequência de DNA , Ligação Viral
17.
Proc Natl Acad Sci U S A ; 111(52): 18655-60, 2014 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-25453089

RESUMO

Horses, asses, and zebras belong to a single genus, Equus, which emerged 4.0-4.5 Mya. Although the equine fossil record represents a textbook example of evolution, the succession of events that gave rise to the diversity of species existing today remains unclear. Here we present six genomes from each living species of asses and zebras. This completes the set of genomes available for all extant species in the genus, which was hitherto represented only by the horse and the domestic donkey. In addition, we used a museum specimen to characterize the genome of the quagga zebra, which was driven to extinction in the early 1900s. We scan the genomes for lineage-specific adaptations and identify 48 genes that have evolved under positive selection and are involved in olfaction, immune response, development, locomotion, and behavior. Our extensive genome dataset reveals a highly dynamic demographic history with synchronous expansions and collapses on different continents during the last 400 ky after major climatic events. We show that the earliest speciation occurred with gene flow in Northern America, and that the ancestor of present-day asses and zebras dispersed into the Old World 2.1-3.4 Mya. Strikingly, we also find evidence for gene flow involving three contemporary equine species despite chromosomal numbers varying from 16 pairs to 31 pairs. These findings challenge the claim that the accumulation of chromosomal rearrangements drive complete reproductive isolation, and promote equids as a fundamental model for understanding the interplay between chromosomal structure, gene flow, and, ultimately, speciation.


Assuntos
Cromossomos de Mamíferos/genética , Equidae/genética , Evolução Molecular , Extinção Biológica , Fluxo Gênico , África , Animais , América do Norte
18.
J Virol ; 86(22): 12407-10, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22933293

RESUMO

We investigated the correlation between in vitro susceptibility of CD3(+) T lymphocytes to equine arteritis virus (EAV) infection and establishment of persistent infection among 14 stallions following natural infections. The data showed that carrier stallions with a CD3(+) T lymphocyte susceptibility phenotype to in vitro EAV infection may be at higher risk of becoming carriers than those that lack this phenotype (P = 0.0002).


Assuntos
Infecções por Arterivirus/virologia , Complexo CD3/biossíntese , Equartevirus/metabolismo , Doenças dos Cavalos/virologia , Linfócitos T/virologia , Animais , Infecções por Arterivirus/metabolismo , Infecções por Arterivirus/transmissão , Portador Sadio/veterinária , Predisposição Genética para Doença , Haplótipos , Cavalos , Técnicas In Vitro , Masculino , Microscopia de Fluorescência/métodos , Fenótipo , Risco
20.
J Virol ; 85(24): 13174-84, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21994447

RESUMO

Previously, we have shown that horses could be divided into susceptible and resistant groups based on an in vitro assay using dual-color flow cytometric analysis of CD3+ T cells infected with equine arteritis virus (EAV). Here, we demonstrate that the differences in in vitro susceptibility of equine CD3+ T lymphocytes to EAV infection have a genetic basis. To investigate the possible hereditary basis for this trait, we conducted a genome-wide association study (GWAS) to compare susceptible and resistant phenotypes. Testing of 267 DNA samples from four horse breeds that had a susceptible or a resistant CD3+ T lymphocyte phenotype using both Illumina Equine SNP50 BeadChip and Sequenom's MassARRAY system identified a common, genetically dominant haplotype associated with the susceptible phenotype in a region of equine chromosome 11 (ECA11), positions 49572804 to 49643932. The presence of a common haplotype indicates that the trait occurred in a common ancestor of all four breeds, suggesting that it may be segregated among other modern horse breeds. Biological pathway analysis revealed several cellular genes within this region of ECA11 encoding proteins associated with virus attachment and entry, cytoskeletal organization, and NF-κB pathways that may be associated with the trait responsible for the in vitro susceptibility/resistance of CD3+ T lymphocytes to EAV infection. The data presented in this study demonstrated a strong association of genetic markers with the trait, representing de facto proof that the trait is under genetic control. To our knowledge, this is the first GWAS of an equine infectious disease and the first GWAS of equine viral arteritis.


Assuntos
Infecções por Arterivirus/veterinária , Equartevirus/imunologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Doenças dos Cavalos/genética , Doenças dos Cavalos/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Infecções por Arterivirus/genética , Infecções por Arterivirus/imunologia , Infecções por Arterivirus/virologia , Complexo CD3/análise , Equartevirus/patogenicidade , Marcadores Genéticos , Haplótipos , Doenças dos Cavalos/virologia , Cavalos , Subpopulações de Linfócitos T/química , Subpopulações de Linfócitos T/virologia
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