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exosomes, endogenous retroviruses and toll-like receptors: pregnancy recognition in ewes.conceptus-endometrial communication during the peri-implantation period of pregnancy ensures establishment of pregnancy. we hypothesized that this dialog involves exosomes, ovine endogenous jaagsiekte retroviruses (enjsrv) and toll-like receptors (tlr) which regulate the secretion of interferon tau (ifnt), the pregnancy recognition signal in ruminants. first, exosomes isolated from uterine flushings from cyclic and pregnant ewes were analyzed for exosomal content and uterine expression of heat s ...201525526899
a sorting signal suppresses ifitm1 restriction of viral entry.the interferon-induced transmembrane proteins (ifitms) broadly inhibit virus infections, particularly at the viral entry level. however, despite this shared ability to inhibit fusion, ifitms differ in the potency and breadth of viruses restricted, an anomaly that is not fully understood. here, we show that differences in the range of viruses restricted by ifitm1 are regulated by a c-terminal non-canonical dibasic sorting signal krxx that suppresses restriction of some viruses by governing its in ...201425527505
[cloning and sequencing analyses of the complete genome of the provirus of the inner-mongolia pandemic strain of the jaagsiekte sheep retrovirus].to investigate the kinship between the inner mongolia pandemic strain and representative strains of the jaagsiekte sheep retrovirus (jsrv), total dna from the lung tissue of a jsrv-infected sheep in inner mongolia was used to clone fragments of gag, pro and pol genes. the recombinant plasmid pmd-jsrv (including complete genomic sequence of the jsrv strain isolated from inner mongolia) was constructed by linking all the cloned fragments with long terminal repeat (ltr) and env gene fragments (clon ...201425562959
the use of endogenous retroviruses as markers to describe the genetic relationships among local swedish sheep breeds.the aim of this study was to describe the genetic relationships among five swedish sheep breeds using insertional polymorphisms of six endogenous jaagsiekte retroviruses of sheep. although the swedish breeds were found to have genomes of 'primitive' origin, there also are indications of the presence of more recently derived sheep breeds within the ancestries of three of the breeds.201525644015
jaagsiekte sheep retrovirus infection of lung slice cultures.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa), a transmissible neoplastic disease of sheep. opa is an economically important veterinary disease and is also a valuable naturally occurring animal model of human lung cancer, with which it shares a similar histological appearance and the activation of common cell signaling pathways. interestingly, the jsrv env protein is directly oncogenic and capable of driving cellular transformation in vivo and ...201525889156
early steps of jaagsiekte sheep retrovirus-mediated cell transformation involve the interaction between env and the ralbp1 cellular protein.ovine pulmonary adenocarcinoma is a naturally occurring lung cancer in sheep induced by the jaagsiekte sheep retrovirus (jsrv). its envelope glycoprotein (env) carries oncogenic properties, and its expression is sufficient to induce in vitro cell transformation and in vivo lung adenocarcinoma. the identification of cellular partners of the jsrv envelope remains crucial for deciphering mechanisms leading to cell transformation. we initially identified ralbp1 (rala binding protein 1; also known as ...201526041289
the roles of syncytin-like proteins in ruminant placentation.recent developments in genome sequencing techniques have led to the identification of huge numbers of endogenous retroviruses (erv) in various mammals. ervs, which occupy 8%-13% of mammalian genomes, are believed to affect mammalian evolution and biological diversity. although the functional significance of most ervs remains to be elucidated, several ervs are thought to have pivotal roles in host physiology. we and other groups recently identified erv envelope proteins (e.g., fematrin-1, syncyti ...201526057168
role for a zinc finger protein (zfp111) in transformation of 208f rat fibroblasts by jaagsiekte sheep retrovirus envelope protein.the native envelope gene (env) of jaagsiekte sheep retrovirus (jsrv) also acts as an oncogene. to investigate the mechanism of transformation, we performed yeast 2-hybrid screening for cellular proteins that interact with env. among several candidates, we identified mouse or rat zinc finger protein 111 (zfp111). the interaction between env and zfp111 was confirmed through in vivo coimmunoprecipitation assays. knockdown of endogenous zfp111 caused a decrease in cell transformation by jsrv env, wh ...201526246563
advances in the study of transmissible respiratory tumours in small ruminants.sheep and goats are widely infected by oncogenic retroviruses, namely jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumour virus (entv). under field conditions, these viruses induce transformation of differentiated epithelial cells in the lungs for jaagsiekte sheep retrovirus or the nasal cavities for enzootic nasal tumour virus. as in other vertebrates, a family of endogenous retroviruses named endogenous jaagsiekte sheep retrovirus (enjsrv) and closely related to exogenous jaagsiekte s ...201526340900
snps in candidate genes mx dynamin-like gtpase and chemokine (c-c motif) receptor-5 are associated with ovine pulmonary adenocarcinoma progression in latxa sheep.ovine pulmonary adenocarcinoma (opa) is a contagious lung cancer in sheep caused by jaagsiekte sheep retrovirus (jsrv). opa is present in many sheep-rearing countries causing economic and welfare issues, as currently no efficient vaccines or treatments are available. breed differences suggest a host genetic component may influence the pathogenesis of opa, but so far few genes have been identified. in this work, a genetic association study was carried out in latxa dairy sheep which were classifie ...201526365162
assessment of transthoracic ultrasound diagnosis of ovine pulmonary adenocarcinoma in adult sheep.ovine pulmonary adenocarcinoma (opa), caused by jaagsiekte sheep retrovirus (jsrv), is a disease of increasing concern in the sheep industry. there is no commercial antemortem test for opa; therefore, an early evaluation phase study was undertaken to examine the accuracy of transthoracic ultrasound examination using a 5-6.5 mhz sector ultrasound machine widely available in veterinary practice in the uk to diagnose opa. restraint, preparation and examination time was restricted to five minutes pe ...201526442526
[pathological diagnoses and whole-genome sequence analyses of the jaagsiekte sheep retrovirus in xinjiang, china].to carry out pathologic diagnoses and whole-genome sequence analyses of the jaagsiekte sheep retrovirus (jsrv) in xinjiang, china, we first observed sheep suspected to have the jsrv. then, the extracted virus suspension was observed by transmission electron microscopy (tem). total rnas from lungs of jsrv-infected sheep were extracted and reverse-transcribed using a cdna synthesis kit. six pairs of primers were designed according to the exogenous reference virus strain (af105220). reverse transcr ...201526470525
the human endogenous retrovirus k(hml-2) has a broad envelope-mediated cellular tropism and is prone to inhibition at a post-entry, pre-integration step.the herv-k(hml-2) family is the most recent addition to the collection of human endogenous retroviruses. it comprises proviruses that encode functional proteins that can assemble into replication defective particles carrying the envelope protein. using a reconstituted herv-k113 envelope sequence, we have analyzed its ability to mediate entry into a set of 33 cell lines from 10 species. of these, 30 were permissive, demonstrating an amphotropism consistent with a broad expression of receptor prot ...201626517399
no evidence for viral sequences in five lepidic adenocarcinomas (former "bac") by a high-throughput sequencing approach.the hypothesis of an infectious etiology of the formerly named bronchiolo-alveolar carcinoma (bac) has raised controversy. we investigated tumor lung tissues from five patients with former bac histology using high-throughput sequencing technologies to discover potential viruses present in this type of lung cancer. around 180 million single reads of 100 bases were generated for each bac sample.201526667652
correction for vigdorovich et al., expression and characterization of a soluble, active form of the jaagsiekte sheep retrovirus receptor, hyal2. 201626822597
lack of association between polymorphic copies of endogenous jaagsiekte sheep retrovirus (enjsrvs) and ovine pulmonary adenocarcinoma.ovine pulmonary adenocarcinoma (opa) is a retrovirus-induced lung tumor of sheep, goat and mouflon, and its etiologic agent, jaagsiekte sheep retrovirus (jsrv) is the only virus known to cause a naturally occurred lung adenocarcinoma. the oncogenic jsrv has several endogenous counterparts termed enjsrvs, some of which have been shown to interfere with jsrv replication at early and late stages of the retroviral cycle inhibiting jsrv exit from the cell, and thus, protecting sheep against the infec ...201626931391
establishment and characterization of a telomerase-immortalized sheep trophoblast cell line.the primary sheep trophoblast cells (stcs) have a finite lifespan in culture. this feature limits the scope for long-term in vitro studies with stcs. this study was an attempt to establish and characterize a telomerase-immortalized sheep trophoblast cell line. stcs were isolated and purified by using percoll and specific immunoaffinity purification, respectively. the purified stcs were transfected with a plasmid carrying sequences of human telomerase reverse transcriptase (htert) to create immor ...201626998488
expression of p53 protein, jaagsiekte sheep retrovirus matrix protein, and surfactant protein in the lungs of sheep with pulmonary adenomatosis.ovine pulmonary adenocarcinoma (opa) is a naturally occurring cancer in sheep that is caused by the jaagsiekte sheep retrovirus (jsrv). because the pathologic and epidemiologic features of opa are similar to those of bronchoalveolar carcinoma in humans, opa is considered a useful animal model for pulmonary carcinogenesis. in this study, 3,512 lungs from various breeds of sheep were collected and macroscopically examined. opa was identified in 30 sheep, and samples of these animals were further e ...201627016721
jaagsiekte sheep retrovirus can reach peyer's patches and mesenteric lymph nodes of lambs nursed by infected mothers.ovine pulmonary adenocarcinoma (opa) is a contagious lung cancer of sheep caused by jaagsiekte sheep retrovirus (jsrv). it is generally accepted that transmission by the respiratory route occurs under natural conditions. however recent studies strongly indicate that jsrv can also be transmitted to lambs perinatally via colostrum and milk (c/m). the aim of this work was to confirm that c/m can transmit jsrv infection to lambs under natural conditions and investigate the initial events associated ...201627154541
detection of jaagsiekte sheep retrovirus in the peripheral blood during the pre-clinical period of ovine pulmonary adenomatosis.the envelope protein (env) of the jaagsiekte sheep retrovirus (jsrv) is known to be a unique oncoprotein responsible for inducing ovine pulmonary adenocarcinoma (opa). the objective of this study was to prepare a specific monoclonal antibody (mab) against the jsrv env protein using bioinformatic analysis. according to the structure and epitope prediction results of jsrv env, the jsrv-env572-615 antigen was prepared via peptide synthesis (amino acid sequence 572-615, denoted as jsrv-env572-615). ...201627706644
truncation of the enzootic nasal tumor virus envelope protein cytoplasmic tail increases env-mediated fusion and infectivity.enzootic nasal tumor virus (entv) and jaagsiekte sheep retrovirus (jsrv) are highly related ovine betaretroviruses that induce nasal and lung tumours in small ruminants, respectively. while the entv and jsrv envelope (env) glycoproteins mediate virus entry using the same cellular receptor, the glycosylphosphatidylinositol-linked protein hyaluronoglucosaminidase, entv env pseudovirions mediate entry into cells from a much more restricted range of species than do jsrv env pseudovirions. unlike jsr ...201727902399
construction of a molecular clone of ovine enzootic nasal tumor virus.enzootic nasal tumor virus (entv-1) is an ovine betaretrovirus that has been linked to enzootic nasal adenocarcinoma (ena), a contagious tumor of the ethmoid turbinates of sheep. transmission experiments performed using virus isolated from cell free nasal tumor homogenates suggest that entv-1 is the causative agent of ena; however, this etiological relationship has not been conclusively proven due to the fact that the virus cannot be propagated in vitro nor is there an infectious molecular clone ...201628038674
evidence against a role for jaagsiekte sheep retrovirus in human lung cancer.jaagsiekte sheep retrovirus (jsrv) causes a contagious lung cancer in sheep and goats that can be transmitted by aerosols produced by infected animals. virus entry into cells is initiated by binding of the viral envelope (env) protein to a specific cell-surface receptor, hyal2. unlike almost all other retroviruses, the jsrv env protein is also a potent oncoprotein and is responsible for lung cancer in animals. of concern, hyal2 is a functional receptor for jsrv in humans.201728107820
modulation of autophagy in exjsrv-env-transfected cells through the akt/mtor and mapk signaling pathway.the envelope (env) of jaagsiekte sheep retrovirus (jsrv) is an oncoprotein of ovine pulmonary adenocarcinoma (opa). autophagy is involved in different cancers, but how it is carcinogenic in jsrv env is unclear. modulation of autophagy in exjsrv-env-nm-transfected cells through the akt/mtor and mapk signaling pathway was studied, and we observed strong positive labeling of p-akt, p-mtor, p-mek1/2, p-erk1/2, p-p38 and p-jnk in tumor cells and typical type ii pneumocytes in naturally infected opa l ...201728235485
characterization of a transgenic mouse model exhibiting spontaneous lung adenocarcinomas with a metastatic phenotype.developing lung cancer in mouse models that display similarities of both phenotype and genotype will undoubtedly provide further and better insights into lung tumor biology. moreover, a high degree of pathophysiological similarity between lung tumors from mouse models and their human counterparts will make it possible to use these mouse models for preclinical tests. ovine pulmonary adenocarcinomas (opas) present the same symptoms as adenocarcinomas in humans and are caused by a betaretrovirus. o ...201728419107
endogenous retroviral insertions indicate a secondary introduction of domestic sheep lineages to the caucasus and central asia between the bronze and iron age.sheep were one of the first livestock species domesticated by humans. after initial domestication in the middle east they were spread across eurasia. the modern distribution of endogenous jaagsiekte sheep retrovirus insertions in domestic sheep breeds suggests that over the course of millennia, successive introductions of improved lineages and selection for wool quality occurred in the mediterranean region and most of asia. here we present a novel ancient dna approach using data of endogenous re ...201728632161
a human endogenous retrovirus-derived gene that can contribute to oncogenesis by activating the erk pathway and inducing migration and invasion.endogenous retroviruses are cellular genes of retroviral origin captured by their host during the course of evolution and represent around 8% of the human genome. although most are defective and transcriptionally silenced, some are still able to generate retroviral-like particles and proteins. among these, the herv-k(hml2) family is remarkable since its members have amplified relatively recently and many of them still have full length coding genes. furthermore, they are induced in cancers, espec ...201728651004
stereological and biophysical characteristics of the ovine surfactant system and its changes caused by ovine pulmonary adenocarcinoma.surfactant covers the inner surface of lung alveoli and lowers the surface tension to prevent alveoli from collapsing. a lack of surfactant or its dysfunction causes dyspnea. the jaagsiekte sheep retrovirus (jsrv) causes ovine pulmonary adenocarcinoma (opa), whose typical clinical appearance is fluid running from nostrils. this fluid might contain surfactant as alveolar type ii pneumocytes (aeii) are target cells for jsrv. therefore, the progressive dyspnea during opa might be caused partially b ...201728651195
full-length genome sequence analysis of enzootic nasal tumor virus isolated from goats in china.enzootic nasal tumor virus (entv) is a betaretrovirus of sheep (entv-1) and goats (entv-2) associated with neoplastic transformation of epithelial cells of the ethmoid turbinate. confirmation of the role of entv in the pathogenesis of enzootic nasal adenocarcinoma (ena) has yet to be resolved due to the inability to culture the virus. very little is known about the prevalence of this disease, particularly in china.201728747230
old origin of a protective endogenous retrovirus (enjsrv) in the ovis genus.sheep, the jaagsiekte sheep retrovirus (jsrv) and its endogenous forms (enjsrvs) are a good model to study long-time relationships between retroviruses and their hosts. taking advantage of 76 whole genome resequencing data of wild and domestic ovis, we investigated the evolution of this relationship. an innovative analysis of re-sequencing data allowed characterizing 462 enjsrvs insertion sites (including 435 newly described insertions) in the ovis genus. we focused our study on endogenous copie ...201929976957
jsrv intragenic enhancer element increases expression from a heterologous promoter and promotes high level aav-mediated transgene expression in the lung and liver of mice.jaagsiekte sheep retrovirus (jsrv) induces tumors in the distal airways of sheep and goats. a putative intragenic enhancer, termed je, localized to the 3' end of the jsrv env gene, has been previously described. herein we provide further evidence that the je functions as a transcriptional enhancer, as it was able to enhance gene expression when placed in either forward or reverse orientation when combined with a heterologous chicken beta actin promoter. we then generated novel composite promoter ...202033172105
endogenous retroviruses drive resistance and promotion of exogenous retroviral homologs.endogenous retroviruses (ervs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ervs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. a subset of ervs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (xrv) progenitors. in these cases, erv-xrv interactions have been documented and include (a) recombination to result ...202033290087
insertion of an endogenous jaagsiekte sheep retrovirus element into the bco2 - gene abolishes its function and leads to yellow discoloration of adipose tissue in norwegian spælsau (ovis aries).the accumulation of carotenoids in adipose tissue leading to yellow fat is, in sheep, a heritable recessive trait that can be attributed to a nonsense mutation in the beta-carotene oxygenase 2 (bco2) gene. however, not all sheep breeds suffering from yellow fat have this nonsense mutation, meaning that other functional mechanisms must exist. we investigated one such breed, the norwegian spælsau.202134193038
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