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expression of the jaagsiekte sheep retrovirus envelope glycoprotein is sufficient to induce lung tumors in sheep.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa). the expression of the jsrv envelope (env) alone is sufficient to transform a variety of cell lines in vitro and induce lung cancer in immunodeficient mice. in order to determine the role of the jsrv env in opa tumorigenesis in sheep, we derived a jsrv replication-defective virus (js-rd) which expresses env under the control of its own long terminal repeat (ltr). js-rd was produced by transiently tr ...200616873259
mutational analysis of the cytoplasmic tail of jaagsiekte sheep retrovirus envelope protein.jaagsiekte sheep retrovirus (jsrv) is the etiologic agent of a transmissible lung cancer in sheep, ovine pulmonary adenocarcinoma. jsrv is unique in that the envelope protein functions as an oncogene, since it can morphologically transform fibroblast and epithelial cells in culture and can induce lung tumors in mice. previous studies indicated that the transmembrane (tm) protein is essential for transformation, and particular attention has focused on a yxxm motif in the cytoplasmic tail. in this ...200616873263
oncogenic transformation by the jaagsiekte sheep retrovirus envelope protein.retroviruses have played profound roles in our understanding of the genetic and molecular basis of cancer. jaagsiekte sheep retrovirus (jsrv) is a simple retrovirus that causes contagious lung tumors in sheep, known as ovine pulmonary adenocarcinoma (opa). intriguingly, opa resembles pulmonary adenocarcinoma in humans, and may provide a model for this frequent human cancer. distinct from the classical mechanisms of retroviral oncogenesis by insertional activation of or virus capture of host onco ...200716909114
envelope proteins of jaagsiekte sheep retrovirus and enzootic nasal tumor virus induce similar bronchioalveolar tumors in lungs of mice.jaagsiekte sheep retrovirus (jsrv) induces bronchioalveolar tumors in sheep and goats. expression of the jsrv envelope (env) protein in mouse airway epithelial cells induces similar tumors, indicating that env expression is sufficient for tissue-specific tumor formation. enzootic nasal tumor virus (entv) is related to jsrv but induces tumors in the nasal epithelium of sheep and goats. here we found that entv env can also induce tumors in mice but, unexpectedly, with a phenotype identical to that ...200616940543
fusogenicity of jaagsiekte sheep retrovirus envelope protein is dependent on low ph and is enhanced by cytoplasmic tail truncations.jaagsiekte sheep retrovirus (jsrv) envelope (env) is an active oncogene responsible for neoplastic transformation in animals and cultured cells. in this study, we used syncytium induction and fluorescence-based cell fusion assays to investigate jsrv env fusion and its modulation by the cytoplasmic tail (ct). we found that jsrv env induced syncytia in cells overexpressing the receptor for jsrv and that a low ph was required for this process to occur. fusion kinetics studies revealed that cell-cel ...200818094165
endogenous retroviruses regulate periimplantation placental growth and differentiation.endogenous retroviruses (ervs) are fixed and abundant in the genomes of vertebrates. circumstantial evidence suggests that ervs play a role in mammalian reproduction, particularly placental morphogenesis, because intact erv envelope genes were found to be expressed in the syncytiotrophoblasts of human and mouse placenta and to elicit fusion of cells in vitro. we report here in vivo and in vitro experiments finding that the envelope of a particular class of ervs of sheep, endogenous jaagsiekte sh ...200616980413
tumors in mice transgenic for the envelope protein of jaagsiekte sheep retrovirus.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa), a contagious lung cancer in sheep. previous studies have shown that the jsrv envelope protein (env) functions as an oncogene, in that it can morphologically transform rodent fibroblast and epithelial cell lines. to obtain a small animal model for jsrv-induced opa, we generated a transgene expressing an epitope-tagged jsrv env under control of the lung-specific surfactant protein a (spa) promoter. t ...200717043760
the transdominant endogenous retrovirus enjs56a1 associates with and blocks intracellular trafficking of jaagsiekte sheep retrovirus gag.the sheep genome harbors approximately 20 endogenous retroviruses (enjsrvs) highly related to the exogenous jaagsiekte sheep retrovirus (jsrv). one of the enjsrv loci, enjs56a1, acts as a unique restriction factor by blocking jsrv in a transdominant fashion at a late stage of the retroviral cycle. to better understand the molecular basis of this restriction (termed jlr, for jsrv late restriction), we functionally characterized jsrv and enjs56a1 gag proteins. we identified the putative jsrv gag m ...200717135320
infection of lung epithelial cells and induction of pulmonary adenocarcinoma is not the most common outcome of naturally occurring jsrv infection during the commercial lifespan of sheep.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa). in this study, we followed over a 31-month period the natural transmission of jsrv in adult sheep and in their offspring. we established groups derived from flocks with either a high or low incidence of opa and monitored virus transmission, clinical disease and macroscopic/microscopic lung lesions at necropsy. results obtained show that (i) jsrv infection can occur perinatally or in the first few m ...200515950254
amino acid residues that are important for hyal2 function as a receptor for jaagsiekte sheep retrovirus.infection by jaagsiekte sheep retrovirus (jsrv) and by enzootic nasal tumor virus (entv) depends on cell-surface expression of the virus entry receptor, hyaluronidase 2 (hyal2). human hyal2 binds the envelope (env) proteins of these viruses and is functional as a receptor, but hyal2 from mice does not bind env nor does it mediate entry of either virus. here we have explored the amino acid determinants that account for the difference in receptor function.200516191204
jaagsiekte sheep retrovirus-specific immune responses induced by vaccination: a comparison of immunisation strategies.jaagsiekte sheep retrovirus (jsrv) is the aetiological agent of ovine pulmonary adenocarcinoma (opa). no jsrv-specific immunological responses have been detected in clinical cases of opa or in experimentally infected lambs. the aim of the present study was to induce immune responses in sheep against jsrv proteins using several immunisation strategies. the vaccines were administered subcutaneously and intradermally, or intranasally, in adjuvant. antibodies were measured by elisa and immunoblottin ...200616289765
[enzootic nasal adenocarcinoma in a dairy sheep flock].in a herd of dairy sheep several losses occurred due to a respiratory syndrome in combination with progressive wasting. clinical and pathomorphological diagnostics of 3 sheep revealed the presence of cancerous masses in the nasal cavities. these neoplasms were identified as adenocarcinomas originating from the nasal mucosa. etiologically, they were attributed to jrsv (jaagsiekte sheep retrovirus) by detection of capsid protein 24 in western blot. the significance of the disease in switzerland is ...200818605021
multiclonal pattern of jaagsiekte sheep retrovirus integration sites in ovine pulmonary adenocarcinoma.insertional mutagenesis and envelope (env)-mediated oncogenesis are hypothesized mechanisms by which jaagsiekte sheep retrovirus (jsrv) causes ovine pulmonary adenocarcinoma (opa). twenty-eight jsrv integration sites in lung tumors (lts) from four sheep with opa were cloned and sequenced by a multiple step gene walking technique. using nested pcr, clonal expansion of these integration sites could be detected, if at all, only in the localized regions of lt from which the integration sites were de ...200616310879
eradication of ovine pulmonary adenocarcinoma by motherless rearing of lambs.the principles of maedi-visna eradication programmes were applied to a field trial for the eradication of ovine pulmonary adenocarcinoma (opa). in two maternal flocks the prevalence of gross and histological lesions in slaughtered animals was 18.3 per cent and 29.8 per cent, respectively. the lambing period was supervised for three consecutive years from 1999 to 2001, during which the lambs were taken away from their mothers at birth, deprived of maternal colostrum, and hand-reared away from oth ...200717660466
mechanisms of late restriction induced by an endogenous retrovirus.the host has developed during evolution a variety of "restriction factors" to fight retroviral infections. we investigated the mechanisms of a unique viral block acting at late stages of the retrovirus replication cycle. the sheep genome is colonized by several copies of endogenous retroviruses, known as enjsrvs, which are highly related to the oncogenic jaagsiekte sheep retrovirus (jsrv). enjs56a1, one of the enjsrv proviruses, can act as a restriction factor by blocking viral particles release ...200717699582
bronchioloalveolar carcinoma not related to jaagsiekte sheep retrovirus in a goat.a spontaneous lung tumor in a 5-year-old goat of the murciano-granadina breed is described in this paper. clinical signs of cachexia and tachypnoea were evident, and a considerable amount of white mucous foamy fluid was discharged from the nostrils when the animal's head was lowered. a lung tumor with the characteristics of bronchioloalveolar carcinoma was detected during histopathologic examination. the tumor cells were positive for surfactant proteins c and b, confirming that alveolar type ii ...200717846248
jaagsiekte sheep retrovirus is not detected in human lung adenocarcinomas expressing antigens related to the gag polyprotein of betaretroviruses.a proportion of human lung adenocarcinomas (hlacs) express an antigen related to the major capsid protein (ca) of jaagsiekte sheep retrovirus (jsrv), a betaretrovirus that causes a transmissible lung cancer in sheep. in this study, we have investigated whether jsrv or related betaretroviruses are expressed in hlacs. results obtained indicate that jsrv is not associated with human lung adenocarcinomas. however, a proportion of hlacs reacted positively in immunohistochemistry with antibodies speci ...200717889995
a large animal model to evaluate the effects of hsp90 inhibitors for the treatment of lung adenocarcinoma.ovine pulmonary adenocarcinoma (opa) is a naturally occurring lung cancer of sheep caused by jaagsiekte sheep retrovirus (jsrv). the jsrv envelope glycoprotein (env) functions as a dominant oncoprotein in vitro and in vivo. in order to develop the basis for the use of opa as a lung cancer model, we screened a variety of signal transduction inhibitors for their ability to block transformation by the jsrv env. most inhibitors were not effective in blocking jsrv env-induced transformation. on the c ...200817961623
a paradigm for virus-host coevolution: sequential counter-adaptations between endogenous and exogenous retroviruses.endogenous retroviruses (ervs) are remnants of ancient retroviral infections of the host germline transmitted vertically from generation to generation. it is hypothesized that some ervs are used by the host as restriction factors to block the infection of pathogenic retroviruses. indeed, some ervs efficiently interfere with the replication of related exogenous retroviruses. however, data suggesting that these mechanisms have influenced the coevolution of endogenous and/or exogenous retroviruses ...200717997604
specific in vivo expression in type ii pneumocytes of the jaagsiekte sheep retrovirus long terminal repeat in transgenic mice.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma, a transmissible lung cancer in sheep. previous experiments in differentiated murine tissue culture cell lines suggested that the disease specificity of jsrv for secretory lung epithelial cells (type ii pneumocytes an clara cells) reflects transcriptional specificity of the viral long terminal repeat (ltr) for these cells. to test this in vivo, transgenic mice carrying the bacterial beta-galactosidase (be ...200818054063
jaagsiekte sheep retrovirus utilizes a ph-dependent endocytosis pathway for entry.using moloney murine leukemia virus pseudovirions bearing the envelope protein of jaagsiekte sheep retrovirus (jsrv), we report here that entry was weakly inhibited by lysosomotropic agents but was profoundly blocked by bafilomycin a1 (bafa1). kinetics studies revealed that jsrv entry is a slow process and was substantially blocked by a dominant-negative mutant of dynamin. interestingly, a low-ph pulse overcame the bafa1 block to jsrv infection, although this occurred only if virus-bound cells w ...200818094164
[current views on the mechanism of oncogenic cell transformation in ovine pulmonary adenocarcinoma].lung cancer is the most frequently diagnosed of all the human neoplasms leading to death. because twenty percent of cases are not associated with cigarette smoking, other causes and methods of early diagnosis are being sought. bronchioloalveolar cancer, which is a subtype of the most common primary lung cancer, adenocarcinoma, is very similar to ovine pulmonary adenocarcinoma (opa), a naturally occurring lung cancer in sheep. opa is caused by the virus jaagsiekte sheep retrovirus (jsrv), a membe ...200718097338
signal transduction pathways utilized by enzootic nasal tumor virus (entv-1) envelope protein in transformation of rat epithelial cells resemble those used by jaagsiekte sheep retrovirus.the ovine beta-retroviruses enzootic nasal tumor virus (entv) and jaagsiekte sheep retrovirus (jsrv) are the causative agent of enzootic nasal adenocarcinoma (ena) and ovine pulmonary adenocarcinoma (opa), respectively, characterized by neoplastic transformation of secretory epithelial cells. the envelope (env) proteins of these related betaretroviruses act as oncogenes, in that they can transform fibroblast and epithelial cell lines in culture. in addition, viral vector-mediated expression of t ...200818176837
evaluation of the efficacy of clinical diagnosis of ovine pulmonary adenocarcinoma. 200818204033
presence of jaagsiekte sheep retrovirus in tissue sections from human bronchioloalveolar carcinoma depends on patients' geographical origin. 200818206499
alveolar type ii cells isolated from pulmonary adenocarcinoma: a model for jsrv expression in vitro.ovine pulmonary adenocarcinoma (opa) is a naturally occurring cancer in sheep, with clinical, radiologic, and histopathologic features similar to that of human pneumonic-type bronchioloalveolar carcinoma. jsrv (jaagsiekte sheep retrovirus) is the etiologic agent of this contagious lung cancer in sheep. cells involved in the tumor derive from alveolar type ii cells and clara cells, epithelial cells of the distal respiratory tract. these cells are the major site for viral expression in jsrv-infect ...200717158359
lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (jsrv) closely resembles lung cancer in sheep infected with jsrv.jaagsiekte sheep retrovirus (jsrv) causes a lethal lung cancer in sheep and goats. expression of the jsrv envelope (env) protein in mouse lung, by using a replication-defective adeno-associated virus type 6 (aav6) vector, induces tumors resembling those seen in sheep. however, the mouse and sheep tumors have not been carefully compared to determine if env expression alone in mice can account for the disease features observed in sheep, or whether additional aspects of virus replication in sheep a ...200617177996
colostrum and milk can transmit jaagsiekte retrovirus to lambs.ovine pulmonary adenocarcinoma (opa) is a contagious disease caused by jaagsiekte sheep retrovirus (jsrv). in the three studies performed, we have obtained data of the importance of colostrum/milk (c/m) in the transmission of jsrv. in the first study, a group of sheep from a flock with a long history of opa, samples from colostrum and peripheral blood leucocytes (pbls) were collected. two specific pcrs (u3-ltr and env of the jsrv) were carried out. using u3pcr 8/34 sheep were positive in colostr ...200818328646
ability of hyaluronidase 2 to degrade extracellular hyaluronan is not required for its function as a receptor for jaagsiekte sheep retrovirus.jaagsiekte sheep retrovirus (jsrv) uses hyaluronidase 2 (hyal2) as a cell entry receptor. by making inactivating mutations to the catalytic residues of human hyal2, we found that hyaluronidase activity was dispensable for its receptor function. the affinities of the jsrv envelope glycoprotein for hyal2 and the hyal2 mutant were similar, and hyaluronan did not block either high-affinity interaction or virus infection. while generating the hyal2 mutant, we discovered that our previous analysis of ...200717229709
jaagsiekte sheep retrovirus (jsrv): from virus to lung cancer in sheep.jaagsiekte sheep retrovirus (jsrv) is a betaretrovirus infecting sheep. this virus is responsible for a pulmonary adenocarcinoma, by transformation of epithelial cells from the bronchioli and alveoli. this animal cancer is similar to human bronchioloalveolar cancer (bac), a specific form of human lung cancer for which a viral aetiology has not yet been identified. jsrv interacts with target cells through the membrane receptor hyal2. the jsrv genome is simple and contains no recognised oncogene. ...200717257570
comparison of ltr enhancer elements in sheep beta retroviruses: insights into the basis for tissue-specific expression.jaagsiekte sheep retrovirus (jsrv), enzootic nasal tumor virus (entv), and endogenous sheep retroviruses (esrvs) are highly related sheep betaretroviruses that display different expression profiles in vivo. jsrv and entv are expressed in lungs and nasal adenocarcinomas, respectively, while esrvs are primarily expressed in the reproductive tract of ewes. evidence suggests that the cell tropism of jsrv, entv, and esrvs is due to the transcriptional specificity of the ltrs. we have previously found ...200717268841
pcr examination of bronchoalveolar lavage samples is a useful tool in pre-clinical diagnosis of ovine pulmonary adenocarcinoma (jaagsiekte).ovine pulmonary adenocarcinoma (opa) is a contagious lung tumour of sheep caused by jaagsiekte sheep retrovirus (jsrv). the disease is a particular problem in flocks in many parts of the world. the aim of the study was to assess screening methods for individual animals as a prelude to future eradication trials. results of histological examination were used as the standard to evaluate the relative sensitivity and specificity of an established heminested polymerase chain reaction (pcr) test for js ...200717418304
centrosome and retroviruses: the dangerous liaisons.centrosomes are the major microtubule organizing structures in vertebrate cells. they localize in close proximity to the nucleus for the duration of interphase and play major roles in numerous cell functions. consequently, any deficiency in centrosome function or number may lead to genetic instability. several viruses including retroviruses such as, foamy virus, hiv-1, jsrv, m-pmv and htlv-1 have been shown to hamper centrosome functions for their own profit, but the outcomes are very different. ...200717433108
endogenous jsrv-like proviruses in domestic cattle: analysis of sequences and transcripts.jaagsiekte retrovirus is an exogenous (exjsrv) beta-retrovirus with a simple genome. it causes lower airway epithelial cell tumors in small ruminants. endogenous (enjsrv) counterparts of exjsrv are present in different copy numbers in numerous bovidae family members. this work has focused on enjsrv in simmental (germany) and limousine (france) beef breeds of domestic cattle and domestic goat. of the enjsrv sequences in cattle, the orf-x sequences were about 99% identical, the ltr sequences were ...200717570457
in vivo tumorigenesis by jaagsiekte sheep retrovirus (jsrv) requires y590 in env tm, but not full-length orfx open reading frame.jaagsiekte retrovirus (jsrv) causes ovine pulmonary adenocarcinoma (opa), a transmissible lung cancer of sheep. the envelope (env) glycoprotein protein of jsrv functions as a dominant oncoprotein in vitro and in vivo. an sh2 binding domain (yxxm) in the cytoplasmic tail of the jsrv env is one of the main determinants of viral transformation at least in vitro. in these studies, we report the first in vivo tests of site-specific mutants of jsrv in their natural host, the sheep. we show that, in vi ...200717610928
structure of the capsid amino-terminal domain from the betaretrovirus, jaagsiekte sheep retrovirus.jaagsiekte sheep retrovirus is a betaretrovirus and the causative agent of pulmonary adenocarcinoma, a transmissible lung tumour of sheep. here we report the crystal structure of the capsid amino-terminal domain and examine the self-association properties of jaagsiekte sheep retrovirus capsid. we find that the structure is remarkably similar to the amino-terminal domain of the alpharetrovirus, avian leukosis virus, revealing a previously undetected evolutionary similarity. examination of capsid ...200919007792
immunohistochemical detection of pulmonary surfactant proteins and retroviral antigens in the lungs of sheep with pulmonary adenomatosis.the lungs and mediastinal and bronchial lymph nodes from 26 sheep with ovine pulmonary adenomatosis (opa) were examined. microscopically, the tumour was disseminated throughout the lungs and displayed acinar or papillary growth. the neoplastic cells were cuboidal or columnar with clear cytoplasm and a low mitotic rate. retrovirus antigen (jaagsiekte sheep retrovirus capsid protein, jsrv ca) was demonstrated in the cytoplasm of tumour cells in the lung and lymph nodes by immunohistochemistry. the ...200919081577
jaagsiekte sheep retrovirus is present at high concentration in lung fluid produced by ovine pulmonary adenocarcinoma-affected sheep and can survive for several weeks at ambient temperatures.jaagsiekte sheep retrovirus (jsrv) causes a fatal lung cancer of sheep known as ovine pulmonary adenocarcinoma (opa). opa is a significant disease in many sheep-rearing countries and there is no effective method of control. a unique feature of opa is the overproduction of fluid in the lung of affected animals. this lung fluid contains jsrv and provides a means of transmission through the inhalation of virus. in this study we demonstrated that lung fluid from different opa cases contained between ...200919114283
the signal peptide of a simple retrovirus envelope functions as a posttranscriptional regulator of viral gene expression.retroviruses use different strategies to regulate transcription and translation and exploit the cellular machinery involved in these processes. this study shows that the signal peptide of the envelope glycoprotein (env) of jaagsiekte sheep retrovirus (jsrv) plays a major role in posttranscriptional viral gene expression. expression of the jsrv env in trans increases viral particle production by mechanisms dependent on (i) its leader sequence, (ii) an intact signal peptide cleavage site, (iii) a ...200919244321
[a specific pcr assay and a nested pcr assay for the screening of ovine pulmonary adenomatosis].ovine pulmonary adenomatosis (opa) is a naturally occurring contagious lung tumor of sheep which was caused by an exogenous retrovirus of sheep, jaagsiekte retrovirus (jsrv). although no specific circulating antibodies against the virus coud be detected in infected sheep, exogenous jsrv proviral dna sequences (exjsrv) and jsrv rna transcripts could be detected in lung tumors, lymphoreticular system and peripheral blood mononuclear cells (pbmc) from sheep affected by opa. the sheep genome carried ...200919678567
generation and characterization of jsrv envelope transgenic mice in fvb background.jaagsiekte sheep retrovirus (jsrv) that causes contagious ovine pulmonary adenocarcinoma (opa) in sheep carries an oncogenic envelope gene (env), which is capable of transforming target cells in vitro and in vivo. we cloned full-length jsrv env cdna into an expression vector, spc/sv40, where the transgene was driven by lung-specific surfactant protein c (spc) promoter, to obtain spc-jsrv env construct. spc-jsrv env was microinjected into immunocompetent fvb/n mice embryos to generate env transge ...200919695657
receptor binding and low ph coactivate oncogenic retrovirus envelope-mediated fusion.fusion of enveloped viruses with host cells is triggered by either receptor binding or low ph but rarely requires both except for avian sarcoma leukosis virus (aslv). we recently reported that membrane fusion mediated by an oncogenic jaagsiekte sheep retrovirus (jsrv) envelope (env) requires an acidic ph, yet receptor overexpression is required for this process to occur. here we show that a soluble form of the jsrv receptor, shyal2, promoted jsrv env-mediated fusion at a low ph in normally fusio ...200919726505
jaagsiekte sheep retrovirus encodes a regulatory factor, rej, required for synthesis of gag protein.retroviruses express gag and pol proteins by translation of unspliced genome-length viral rna. for some retroviruses, transport of unspliced viral rna to the cytoplasm is mediated by small regulatory proteins such as human immunodeficiency virus rev, while other retroviruses contain constitutive transport elements in their rnas that allow transport without splicing. in this study, we found that the betaretrovirus jaagsiekte sheep retrovirus (jsrv) encodes within the env gene a trans-acting facto ...200919776124
identification and mutational analysis of a rej response element in jaagsiekte sheep retrovirus rna.jaagsiekte sheep retrovirus (jsrv) is a simple betaretrovirus causing a contagious lung cancer of sheep. jsrv encodes unspliced and spliced viral rnas, among which unspliced rna encodes gag and pol proteins and a singly spliced mrna encodes env protein. in another study we found that jsrv encodes a regulatory protein, rej, that is responsible for synthesis of gag polyprotein from unspliced viral rna. rej is encoded in the 5' end of env, and it enhances nuclear export or accumulation of cytoplasm ...200919776134
friendly viruses: the special relationship between endogenous retroviruses and their host.endogenous retroviruses (ervs) are present in the genome of all vertebrates and have coevolved with their hosts for millions of years. some ervs play a critical role in placental development, contribute to genome plasticity, and protect the host against infection of related pathogenic and exogenous retroviruses, thus some ervs have been positively selected and maintained in the host genome. the sheep genome contains 27 endogenous retroviruses (enjsrvs) related to the pathogenic jaagsiekte sheep ...200919845636
diagnostic accuracy of pcr for jaagsiekte sheep retrovirus using field data from 125 scottish sheep flocks.using a representative sample of scottish sheep comprising 125 flocks, the sensitivity and specificity of pcr for jaagsiekte sheep retrovirus (jsrv) was estimated. by combining and adapting existing methods, the characteristics of the diagnostic test were estimated (in the absence of a gold standard reference) using repeated laboratory replicates. as the results of replicates within the same animal cannot be considered to be independent, the performance of the pcr was calculated at individual re ...201119931475
jaagsiekte sheep retrovirus biology and oncogenesis.jaagsiekte sheep retrovirus (jsrv) is the causative agent of a lung cancer in sheep known as ovine pulmonary adenocarcinoma (opa). the disease has been identified around the world in several breeds of sheep and goats, and jsrv infection typically has a serious impact on affected flocks. in addition, studies on opa are an excellent model for human lung carcinogenesis. a unique feature of jsrv is that its envelope (env) protein functions as an oncogene. the jsrv env-induced transformation or oncog ...201021994634
lung tumor development and spontaneous regression in lambs coinfected with jaagsiekte sheep retrovirus and ovine lentivirus.ovine pulmonary adenocarcinoma (opa) is a naturally occurring and experimentally inducible lung cancer of sheep caused by jaagsiekte sheep retrovirus (jsrv). the first aim of this study was to monitor the development of opa with minimally invasive, real-time observations of animals experimentally infected with jsrv as well as ovine lentivirus (maedi-visna virus). worldwide, simultaneous infection of sheep with these 2 retroviruses is a common occurrence, naturally and experimentally; consequentl ...201020080496
tumorigenesis related to retroviral infections.retroviral infections are considered important risk factors for cancer development in humans since approximately 15-20% of cancer worldwide is caused by an infectious agent. this report discusses the most established oncogenic retroviruses, including human immunodeficiency virus (hiv), human t-cell leukemia virus (htlv-1 and -2), rous sarcoma virus (rsv), abelson murine leukemia virus (a-mulv), moloney murine leukemia virus (m-mulv), murine mammary tumor virus (mmtv), bovine leukemia virus, (blv ...201122112727
pathology and pathogenesis of ovine pulmonary adenocarcinoma.ovine pulmonary adenocarcinoma (opa), also known as jaagsiekte, is a transmissible lung tumour of sheep caused by jaagsiekte sheep retrovirus (jsrv). jsrv induces neoplastic transformation of alveolar and bronchiolar secretory epithelial cells and the resulting tumours can grow to occupy a significant portion of the lung. tumour growth is frequently accompanied by the overproduction of fluid in the lung, which further compromises normal respiration. the period between infection and the appearanc ...201020163805
interplay between ovine bone marrow stromal cell antigen 2/tetherin and endogenous retroviruses.endogenous betaretroviruses (enjsrvs) of sheep are expressed abundantly in the female reproductive tract and play a crucial role in conceptus development and placental morphogenesis. interestingly, the colonization of the sheep genome by enjsrvs is likely still ongoing. during early pregnancy, enjsrv expression correlates with the production of tau interferon (ifnt), a type i ifn, by the developing conceptus. ifnt is the pregnancy recognition signal in ruminants and possesses potent antiviral ac ...201020181686
[receptors for animal retroviruses].diseases caused by animal retroviruses have been recognized since 19th century in veterinary field. most livestock and companion animals have own retroviruses. to disclose the receptors for these retroviruses will be useful for understanding retroviral pathogenesis, developments of anti-retroviral drugs and vectors for human and animal gene therapies. of retroviruses in veterinary field, receptors for the following viruses have been identified; equine infectious anemia virus, feline immunodefici ...200920218331
hyaluronidase 2 and its intriguing role as a cell-entry receptor for oncogenic sheep retroviruses.jaagsiekte sheep retrovirus (jsrv) causes lung adenocarcinoma in sheep and goats, while the closely related enzootic nasal tumor virus (entv) causes nasal tumors in the same species. the envelope (env) protein from either virus can transform fibroblasts and epithelial cells in culture, indicating that the env proteins are responsible for tumorigenesis. however, the primary function of retroviral env proteins is to mediate virus entry into cells by interacting with specific cell-surface receptors ...200818485731
ifitm proteins restrict viral membrane hemifusion.the interferon-inducible transmembrane (ifitm) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. here we provide evidence that ifitm proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. ifitm1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; ifitm2 and i ...201323358889
ifitms restrict the replication of multiple pathogenic viruses.the interferon-inducible transmembrane protein (ifitm) family inhibits a growing number of pathogenic viruses, among them influenza a virus, dengue virus, hepatitis c virus, and ebola virus. this review covers recent developments in our understanding of the ifitm's molecular determinants, potential mechanisms of action, and impact on pathogenesis.201324076421
enzootic nasal tumor virus envelope requires a very acidic ph for fusion activation and infection.enzootic nasal tumor virus (entv) is a close relative of jaagsiekte sheep retrovirus (jsrv), and the two viruses use the same receptor, hyaluronidase 2 (hyal2), for cell entry. we report here that, unlike the jsrv envelope (env) protein, the entv env protein does not induce cell fusion at phs of 5.0 and above but requires a much lower ph (4.0 to 4.5) for fusion to occur. the entry of entv env pseudovirions was substantially inhibited by bafilomycin a1 (bafa1) but was surprisingly enhanced by lys ...200818632865
jaagsiekte sheep retrovirus infects multiple cell types in the ovine lung.ovine pulmonary adenocarcinoma (opa) is a transmissible lung cancer of sheep caused by jaagsiekte sheep retrovirus (jsrv). the details of early events in the pathogenesis of opa are not fully understood. for example, the identity of the jsrv target cell in the lung has not yet been determined. mature opa tumors express surfactant protein-c (sp-c) or clara cell-specific protein (ccsp), which are specific markers of type ii pneumocytes or clara cells, respectively. however, it is unclear whether t ...201121270155
betaretroviral envelope subunits are noncovalently associated and restricted to the mammalian class.the structure of the transmembrane subunit (tm) of the retroviral envelope glycoprotein (env) is highly conserved among most retrovirus genera and includes a pair of cysteines that forms an intramolecular disulfide loop within the ectodomain. alpha-, gamma-, and deltaretroviruses have a third cysteine, adjacent to the loop, which forms a disulfide bond between tm and the surface subunit (su) of env, while lentiviruses, which have noncovalently associated subunits, lack this third cysteine. the b ...201223221553
enhanced proliferation of primary rat type ii pneumocytes by jaagsiekte sheep retrovirus envelope protein.jaagsiekte sheep retrovirus (jsrv) is the causative agent of a contagious lung cancer in sheep. the envelope protein (env) is the oncogene, as it can transform cell lines in culture and induce tumors in animals, although the mechanisms for transformation are not yet clear because a system to perform transformation assays in differentiated type ii pneumocytes does not exist. in this study we report culture of primary rat type ii pneumocytes in conditions that favor prolonged expression of markers ...201121316726
three-dimensional culture of an ovine pulmonary adenocarcinoma-derived cell line results in re-expression of surfactant proteins and jaagsiekte sheep retrovirus.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa) in sheep. a major interest is elucidating the mechanism(s) of transformation by the viral envelope (env) that functions as an oncogene. these studies would benefit from a cell line derived from type ii pneumocytes that have maintained the differentiation state. in this study we used an opa-derived cell line (js7), which has lost structural and functional properties of type ii pneumocytes, and no lon ...201121481432
lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair.jaagsiekte sheep retrovirus (jsrv) is a unique oncogenic virus with distinctive biological properties. jsrv is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, opa) and possessing a major structural protein that functions as a dominant oncoprotein. lung cancer is the major cause of death among cancer patients. opa can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmona ...201121483485
jsrv and entv promoters drive gene expression in all airway epithelial cells of mice but only induce tumors in the alveolar region of the lung.jaagsiekte sheep retrovirus (jsrv) induces tumors in the distal airways of sheep and goats, while the closely-related enzootic nasal tumor viruses (entv-1 and entv-2) induce tumors in the nasal epithelium of sheep and goats, respectively. when expressed using a strong rous sarcoma virus (rsv) promoter, the envelope proteins of these viruses induce tumors in the respiratory tract of mice, but only in the distal airway. to examine the role of the retroviral long terminal repeat (ltr) promoters in ...201121593165
the signal peptide of a recently integrated endogenous sheep betaretrovirus envelope plays a major role in eluding gag-mediated late restriction.the exogenous and pathogenic jaagsiekte sheep retrovirus (jsrv) co-exists with highly related and biologically active endogenous retroviruses (enjsrvs). the endogenous enjs56a1 locus possesses a defective gag polyprotein which blocks the late replication steps of related exogenous and endogenous retroviruses by a mechanism known as jsrv late restriction (jlr). conversely, enjsrv-26, which most likely integrated into the sheep genome less than 200 years ago, is able to escape jlr. in this study, ...201121593182
immunohistochemical and histopathological findings of ovine pulmonary adenocarcinoma (jaagsiekte) in egyptian sheep.ovine pulmonary adenocarcinoma (opa) is a naturally occurring retrovirus-induced transmissible lung cancer in sheep. lungs and associated (bronchial and mediastinal) lymph nodes of seven sheep with opa were examined. lungs had few multifocal consolidated slightly elevated gray to white masses ranging from 0.5 to 3 cm in diameter. histopathologically, these masses appeared as well-differentiated acinar adenocarcinoma with little evidence of anaplasia. the acini composed of well-differentiated cub ...201121626063
jaagsiekte sheep retrovirus pseudotyped lentiviral vector-mediated gene transfer to fetal ovine lung.viral vector-mediated gene transfer to the postnatal respiratory epithelium has, in general, been of low efficiency due to physical and immunological barriers, non-apical location of cellular receptors critical for viral uptake and limited transduction of resident stem/progenitor cells. these obstacles may be overcome using a prenatal strategy. in this study, hiv-1-based lentiviral vectors (lvs) pseudotyped with the envelope glycoproteins of jaagsiekte sheep retrovirus (jsrv-lv), baculovirus gp6 ...201121654824
endogenous retroviruses of sheep: a model system for understanding physiological adaptation to an evolving ruminant genome.endogenous retroviruses (ervs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. the sheep genome contains 27 endogenous betaretroviruses (enjsrvs) related to the exogenous and pathogenic jaagsiekte sheep retrovirus (jsrv), the causative agent of a ...201021755665
surveillance of jaagsiekte sheep retrovirus in sheep in hokkaido, the northern island of japan.surveillance of jaagsiekte sheep retrovirus (jsrv) infection was performed by polymerase chain reaction (pcr) of blood dna samples collected from 40 sheep and goats in 10 different flocks in hokkaido, the northern island of japan. no exogenous (oncogenic) jsrv sequence was detected by the pcr in these samples, while the ovine endogenous retrovirus sequence was successfully amplified in all samples. our paper is the first demonstration of jsrv surveillance in japan, and shows no evidence of oncog ...201121712639
single residues in the surface subunits of oncogenic sheep retrovirus envelopes distinguish receptor-mediated triggering for fusion at low ph and infection.jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv) are two closely related oncogenic retroviruses that share the same cellular receptor yet exhibit distinct fusogenicity and infectivity. here, we find that the low fusogenicity of entv envelope protein (env) is not because of receptor binding, but lies in its intrinsic insensitivity to receptor-mediated triggering for fusion at low ph. distinct from jsrv, shedding of entv surface (su) subunit into culture medium was not enha ...201122018783
jaagsiekte sheep retrovirus transformation in madin-darby canine kidney epithelial cell three-dimensional culture.jaagsiekte sheep retrovirus (jsrv) is the causative agent of a contagious lung cancer in sheep that shares similarities with human bronchioloalveolar carcinoma (bac). jsrv is unique because the envelope gene (env) is the oncogene, as it can transform cells in culture and induce tumors in animals. the phosphatidylinositol 3-kinase (pi3k)-akt-mtor and h/n-ras-mek-mitogen-activated protein kinase (mapk) pathways have been shown to be critical for env transformation. however, the question still rema ...201020219922
endogenous retroviruses in trophoblast differentiation and placental development.endogenous retroviruses (ervs) are present in the genome of all vertebrates and originated from infections of the germline of the host by exogenous retroviruses. ervs have coevolved with their hosts for millions of years and are recognized to contribute to genome plasticity, protect the host against infection of related pathogenic and exogenous retroviruses, and play a vital role in development of the placenta. consequently, some ervs have been positively selected and maintained in the host geno ...201020528833
viral particles of endogenous betaretroviruses are released in the sheep uterus and infect the conceptus trophectoderm in a transspecies embryo transfer model.the sheep genome contains multiple copies of endogenous betaretroviruses highly related to the exogenous and oncogenic jaagsiekte sheep retrovirus (jsrv). the endogenous jsrvs (enjsrvs) are abundantly expressed in the uterine luminal and glandular epithelia as well as in the conceptus trophectoderm and are essential for conceptus elongation and trophectoderm growth and development. of note, enjsrvs are present in sheep and goats but not cattle. at least 5 of the 27 enjsrv loci cloned to date pos ...201020610723
functional interaction between env oncogene from jaagsiekte sheep retrovirus and tumor suppressor sprouty2.jaagsiekte sheep retrovirus (jsrv) is a type d retrovirus capable of transforming target cells in vitro and in vivo. the envelope (env) gene from jsrv and from related retroviruses can induce oncogenic transformation, although the detailed mechanism is yet to be clearly understood. host cell factors are envisaged to play a critical determining role in the regulation of env-mediated cell transformation.201020678191
absence of markers of betaretrovirus infection in human pulmonary adenocarcinoma.a proportion of human pulmonary adenocarcinomas has been shown previously to express an antigen related to the gag protein of a betaretrovirus, jaagsiekte sheep retrovirus, that causes ovine pulmonary adenocarcinoma. to investigate further the hypothesis that a retrovirus might be present in human lung adenocarcinoma, we examined specimens from patients with lung cancer for evidence of retroviral infection by immunohistochemistry, reverse transcriptase-polymerase chain reaction, immunoblotting a ...201020825971
coevolution of endogenous betaretroviruses of sheep and their host.sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. jaagsiekte sheep retrovirus (jsrv) is a pathogenic exogenous retrovirus and the causative agent of ovine pulmonary adenocarcinoma. the sheep genome contains at least 27 copies of endogenous retroviruses (enjsrvs) highly related to jsrv. enjsrvs have played several roles in the evolution of the domestic sheep as they are able to block the jsrv replication cycle and play a criti ...200818818869
paranasal sinus masses of rocky mountain bighorn sheep (ovis canadensis canadensis).this article describes 10 cases of paranasal sinus masses in rocky mountain bighorn sheep (ovis canadensis canadensis). among 21 bighorns that were examined from 11 herds in colorado, 10 individuals (48%) from 4 herds (36%) had masses arising from the paranasal sinuses. affected animals included 9 of 17 females (53%) and 1 of 4 males (25%), ranging in age from approximately 2 years to greater than 10 years. defining gross features of these masses included unilateral or bilateral diffuse thickeni ...201020926735
ovine pulmonary adenocarcinoma as an animal model of progressive lung cancer and the impact of nutritional selenium supply.jaagsiekte sheep retrovirus (jsrv) is known to induce ovine pulmonary adenocarcinoma (opa). several studies have suggested an influence of selenium (se) status on cancer progression. thus, combining opa with a defined se supply might serve as a suitable animal model to study the impact of se on lung cancer progression. 16 naturally jsrv-infected sheep were divided into 2 treatment groups receiving (a) <0.05 and (b) 0.2 mg se/kg dry matter in diet, respectively. computed tomography (ct) was perfo ...201021146969
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
evolutionary dynamics of endogenous jaagsiekte sheep retroviruses proliferation in the domestic sheep, mouflon and pyrenean chamois.the oncogenic exogenous jaagsiekte sheep retrovirus (jsrv), responsible for ovine pulmonary adenocarcinoma, has several endogenous counterparts termed enjsrvs. although many of these elements have been inactivated over time by the accumulation of deleterious mutations or internal recombination leading to solo long terminal repeat (ltr) formation, several members of enjsrvs have been identified as nearly intact and probably represent recent integration events. to determine the level of enjsrv pol ...201424690757
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
host species barriers to jaagsiekte sheep retrovirus replication and carcinogenesis.understanding the factors governing host species barriers to virus transmission has added significantly to our appreciation of virus pathogenesis. jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa), a transmissible lung cancer of sheep that has rarely been found in goats. in this study, in order to further clarify the pathogenesis of opa, we investigated whether goats are resistant to jsrv replication and carcinogenesis. we found that jsrv induces l ...201323903827
"ménage à trois": the evolutionary interplay between jsrv, enjsrvs and domestic sheep.sheep betaretroviruses represent a fascinating model to study the complex evolutionary interplay between host and pathogen in natural settings. in infected sheep, the exogenous and pathogenic jaagsiekte sheep retrovirus (jsrv) coexists with a variety of highly related endogenous jsrvs, referred to as enjsrvs. during evolution, some of them were co-opted by the host as they fulfilled important biological functions, including placental development and protection against related exogenous retroviru ...201425502326
application of next generation sequencing in mammalian embryogenomics: lessons learned from endogenous betaretroviruses of sheep.endogenous retroviruses (ervs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. the sheep genome contains 27 jsrv-related endogenous betaretroviruses (enjsrvs) related to the pathogenic jaagsiekte sheep retrovirus (jsrv) that have been integrating in the host genome for the last 5-7 million years. the exogenous jsrv is a causative agent of a transmissible lung cancer ...201222951118
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
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
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
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
Lung Cancer in Mice Induced by the Jaagsiekte Sheep Retrovirus Envelope Protein Is Not Maintained by Rare Cancer Stem Cells, but Tumorigenicity Does Correlate with Wnt Pathway Activation.JSRV, a simple beta-retrovirus, is the etiologic agent of ovine pulmonary adenocarcinoma, a form of non-small cell lung cancer in sheep and goats. It has been shown that the envelope protein alone is sufficient to induce tumorigenesis in the lungs of mice when delivered via an adeno-associated viral vector. Here, we tested the hypothesis that JSRV envelope-induced tumors are maintained by a small population of tumor-initiating cells, termed cancer stem cells. To test this hypothesis, dissociated ...201122064658
critical role of a leucine-valine change in the distinct low ph requirements for membrane fusion between two related retrovirus envelopes.many viruses use ph-dependent pathway for fusion with host cell membrane, the mechanism of which is still poorly understood. here we report that a subtle leucine (leu) - valine (val) change at position 501 in the envelope glycoproteins (envs) of two related retroviruses, jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv), is responsible for their distinct low ph requirements for membrane fusion and infection. the leu and val residues are predicted to reside within the c-ter ...201222235118
overexpression of aldolase a and cytokeratin 19 in ovine pulmonary adenocarcinoma.ovine pulmonary adenocarcinoma (opa) is a transmissible lung cancer of sheep caused by jaagsiekte sheep retrovirus (jsrv). in the present study the protein profiles of five neoplastic and three non-neoplastic sheep lung tissues were examined for the identification of proteins overexpressed in ovine pulmonary adenocarcinoma. lung sections of the experimental group of sheep were collected during necropsies for proteomic and immunohistochemical examination. two dimensional electrophoresis (2de) was ...201223390760
copy number variation and differential expression of a protective endogenous retrovirus in sheep.the jaagsiekte sheep retrovirus exjsrv and its endogenous counterpart enjsrv co-exist in sheep. exjsrv, a betaretrovirus, is the etiological agent of ovine pulmonary adenocarcinoma, and it has been demonstrated in vitro that an enjsrv gag variant bearing the r-to-w amino acid change at position 21 was able to block exjsrv budding from the cells, providing a potential protective role for the host. in this work, we developed a fast mutation detection assay based on the oligo ligation assay (ola) t ...201222911867
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
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
professional exposure to goats increases the risk of pneumonic-type lung adenocarcinoma: results of the ifct-0504-epidemio study.pneumonic-type lung adenocarcinoma (p-adc) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (jsrv)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to p-adc in humans. our objective was to explore whether exposure to domestic small ruminants may r ...201222655078
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
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
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
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
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
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
biochemical characterization of novel retroviral integrase proteins.integrase is an essential retroviral enzyme, catalyzing the stable integration of reverse transcribed dna into cellular dna. several aspects of the integration mechanism, including the length of host dna sequence duplication flanking the integrated provirus, which can be from 4 to 6 bp, and the nucleotide preferences at the site of integration, are thought to cluster among the different retroviral genera. to date only the spumavirus prototype foamy virus integrase has provided diffractable cryst ...201324124581
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