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nucleotide sequence of the jaagsiekte retrovirus, an exogenous and endogenous type d and b retrovirus of sheep and goats.the complete genome of the jaagsiekte sheep retrovirus (jsrv), the suspected etiological agent of ovine pulmonary carcinoma, has been cloned from viral particles secreted in lung exudates of affected animals and sequenced. the genome is 7,462 nucleotides long and exhibits a genetic organization characteristic of the type b and d oncoviruses. comparison of the amino acid sequences of jsrv proteins with those of other retrovirus proteins and phylogenetic studies suggest that jsrv diverged from its ...19921629959
isolation, identification, and partial cdna cloning of genomic rna of jaagsiekte retrovirus, the etiological agent of sheep pulmonary adenomatosis.the genome of the jaagsiekte (js) retrovirus (jsrv), the etiological agent of sheep pulmonary adenomatosis (jaagsiekte), has been identified, isolated, and partly cloned. the jsrv genome is ca. 8.7 kb long. cdna of the genomic rna was synthesized and cloned. a clone, js 46.1, was isolated and characterized. it has an insert of 2.1 kb which hybridizes to the same 8.7-kb rna in all the jsrv-infected sheep lung washes tested but does not hybridize to maedi-visna virus, a sheep lentivirus often foun ...19911651422
some characteristics of a retrovirus isolated from transformed bovine cells.a novel retrovirus has been isolated from bovine cells transformed after cocultivation with leukocytes from an animal suffering from sheep-associated bovine malignant catarrhal fever. morphologically and in its morphogenesis the virus resembles the type d mason-pfizer monkey virus (mpmv) as well as the ovine jaagsiekte retrovirus (jsrv). it is also serologically related to these two viruses, whereas a relationship to other known bovine retroviruses was not detected. however, its density of 1.16 ...19892763459
biotechnology, viral oncogenesis and jaagsiekte.a brief description is given of the discovery of retroviral and cellular oncogenes and of their putative role in oncogenesis. attempts to apply the biotechnological techniques that were so successful in the study of other retroviruses to the newly-discovered jaagsiekte retrovirus are briefly reviewed.19853003648
isolation and identification of a south african lentivirus from jaagsiekte lungs.in the course of attempts to grow the jaagsiekte retrovirus in cell culture, a typical lentivirus was isolated for the first time in south africa from adenomatous lungs. morphologically the virus could not be distinguished from other lentiviruses, but serologically it was shown to be more closely related to visna virus than to caprine arthritis-encephalitis virus. however, a preliminary restriction enzyme analysis of the linear proviral dna of this new lentivirus (sa-dmvv) revealed that it is si ...19863008059
experimental transmission of jaagsiekte (ovine pulmonary adenomatosis) to goats.jaagsiekte was successfully transmitted to at least 2 out of 6 goats inoculated intratracheally with partially purified jaagsiekte retrovirus. multiple, small, well circumscribed nodules found in the lungs consisted of typical papilliform proliferations of neoplastic type ii epithelial cells. histological evidence of a mild interstitial pneumonia in 4 of the experimental animals can probably be attributed to a contaminating lentivirus in the jaagsiekte retrovirus preparation, as suggested by the ...19883353097
the localization of a mason-pfizer monkey virus-related antigen in jaagsiekte tumour tissue and cell lines.mason-pfizer monkey virus-related antigen was detected in 3 out of 5 jaagsiekte lungs examined using a direct immunoperoxidase staining technique with anti-mpmv p27 serum. most of the antigen was localized in the alveolar lumina of the lesions. the reaction was further characterised on immune blots and found to involve a protein with a molecular mass of 29 000 daltons (jsrv p29). jsrv p29 antigen was also detected in 2 jaagsiekte cell lines.19863523361
isolation and preliminary characterization of the jaagsiekte retrovirus (jsrv).jaagsiekte, or ovine pulmonary adenomatosis, is caused by a recently discovered retrovirus. the virus cannot be cultivated in vitro at present, but a procedure is described for the isolation and purification of small amounts in the form of immune complexes with iga from affected lungs. the virion was shown to possess a 70s rna genome which can be transcribed by an endogenous reverse transcriptase. nine size from 94 000 to 25 000 daltons, were found in purified preparations. using neutralization ...19836676694
the morphology and morphogenesis of jaagsiekte retrovirus (jsrv).jaagsiekte retrovirus ( jsrv ) was recently shown to be the aetiological agent of jaasiekte (ovine pulmonary adenomatosis). the morphogenesis of jsrv was studied in jaagsiekte tumour tissue. intracytoplasmic particles, often associated with centrioles, were found in tumour cells. jsrv budded from tumour cells with a complete core which appeared to mature during the budding process. extracellular particles were found in the alveolar lumen. immature extracellular particles were rare. mature extrac ...19836676695
epithelial tumour cells in the lungs of sheep with pulmonary adenomatosis are major sites of replication for jaagsiekte retrovirus.sheep pulmonary adenomatosis (spa) is a naturally occurring contagious lung tumour of sheep which has been associated aetiologically with a type d- and b-related retrovirus (jaagsiekte retrovirus; jsrv). to improve understanding of the aetio-pathogenesis of spa, the distribution and the sites of jsrv replication in sheep with naturally or experimentally induced spa or in unaffected controls were identified. new immunological reagents were produced and a blocking enzyme-linked immunosorbent assay ...19957595380
analysis of a type d retroviral capsid gene expressed in ovine pulmonary carcinoma and present in both affected and unaffected sheep genomes.ovine pulmonary carcinoma is a contagious neoplastic disease of sheep which can be transmitted experimentally with cell-free filtrate. products homologous to structural proteins of type d and type b retroviruses are expressed in the tumors, but an infectious retrovirus has yet to be isolated. retroviral rna was isolated from an affected peruvian sheep and used as a substrate for reverse transcription. the dna obtained was subjected to polymerase chain reaction amplification using degenerate prim ...19948009860
distribution of endogenous type b and type d sheep retrovirus sequences in ungulates and other mammals.the jaagsiekte sheep retrovirus (jsrv), which appears to be a type b/d retrovirus chimera, has been incriminated as the cause of ovine pulmonary carcinoma. recent studies suggest that the sequences related to this virus are found in the genomes of normal sheep and goats. to learn whether there are breeds of sheep that lack the endogenous viral sequences and to study their distribution among other groups of mammals, we surveyed several domestic sheep and goat breeds, other ungulates, and various ...19968622932
the exogenous form of jaagsiekte retrovirus is specifically associated with a contagious lung cancer of sheep.sheep pulmonary adenomatosis ([spa] ovine pulmonary carcinoma) is a transmissible lung cancer of sheep that has been associated etiologically with a type d- and b-related retrovirus (jaagsiekte retrovirus (jsrv]). to date it has been impossible to cultivate jsrv in vitro and therefore to demonstrate the etiology of spa by a classical approach. in addition, the presence of 15 to 20 copies of endogenous jsrv-related sequences (enjsrv) has hampered studies at the molecular level. the aim of this st ...19968627682
unique long terminal repeat u3 sequences distinguish exogenous jaagsiekte sheep retroviruses associated with ovine pulmonary carcinoma from endogenous loci in the sheep genome.ovine pulmonary carcinoma (opc) is a contagious lung cancer of sheep that is presumed to be caused by an exogenous retrovirus of sheep, jaagsiekte sheep retrovirus (jsrv). the sheep genome carries 15 to 20 copies of endogenous sheep retrovirus (esrv) loci that hybridize to jsrv dna probes. in order to clarity the etiologic roles of esrv and an exogenous jsrv-like retrovirus (exjsrv) in opc, we assessed sequence differences between esrv and jsrv. molecular characterization of six esrv loci reveal ...19968627796
retroviral aetiopathogenesis of ovine pulmonary carcinoma: a critical appraisal.although it has long been thought that a retrovirus is the responsible agent for ovine pulmonary carcinoma (opc), identification of a replicative viral agent has proven difficult. recently, the genome of a new retrovirus, jaagsiekte sheep retrovirus (jsrv), found in the lung-wash of affected sheep lung, has been cloned and sequenced; characterization of this virus and its consistent presence in tumor cells argue for its role as the aetiologic agent of opc. analysis of the nucleic acid sequence o ...19968791848
pcr-based detection and partial characterization of a retrovirus associated with contagious intranasal tumors of sheep and goats.a type d-related retrovirus has been demonstrated in enzootic nasal tumors (ents) of sheep and goats. this retrovirus, ent virus (entv), has antigenic cross-reactivity with the jaagsiekte sheep retrovirus (jsrv), which is associated with a contagious lung tumor of sheep (sheep pulmonary adenomatosis). here, we present the first report of nucleic acid sequence from entv which confirms, at the nucleic acid level, that this retrovirus is related to jsrv yet apparently distinct from it. reverse tran ...19968892877
jaagsiekte retrovirus establishes a disseminated infection of the lymphoid tissues of sheep affected by pulmonary adenomatosis.jaagsiekte retrovirus (jsrv) is an exogenous type d-related retrovirus specifically associated with a contagious lung cancer of sheep (sheep pulmonary adenomatosis; spa). recently, epithelial tumour cells in the lungs of spa-affected sheep were identified as major sites of jsrv replication by immunological techniques and rt-pcr amplification of part of jsrv gag. jsrv was not detected outside the lungs and their draining lymph nodes. however, low levels of jsrv expression in non-respiratory tissu ...19969000089
sheep pulmonary adenomatosis: a unique model of retrovirus-associated lung cancer.sheep pulmonary adenomatosis (spa) is a contagious bronchiolo-alveolar carcinoma of sheep associated with an exogenous type d/b retrovirus known as jaagsiekte sheep retrovirus (jsrv). spa represents a unique model for lung cancer, and studies on its aetiopathogenesis can provide further insight into the mechanisms of epithelial neoplasms.19979447659
lack of a specific immune response against a recombinant capsid protein of jaagsiekte sheep retrovirus in sheep and goats naturally affected by enzootic nasal tumour or sheep pulmonary adenomatosis.enzootic nasal tumour (ent) and sheep pulmonary adenomatosis (spa) are two contagious adenocarcinomas of the respiratory tract of sheep and goats. both diseases are associated with related, but distinct, type-d-retroviruses (entv and jsrv respectively). no evidence of circulating antibodies has been described in animals affected by either ent or spa using antigens from natural sources. we evaluated the usefulness of a recombinant jsrv capsid protein (jsrv-ca) as antigen to study the antibody res ...19989613437
complete sequence of enzootic nasal tumor virus, a retrovirus associated with transmissible intranasal tumors of sheep.the sequence of the complete genome of ovine enzootic nasal tumor virus, an exogenous retrovirus associated exclusively with contagious intranasal tumors of sheep, was determined. the genome is 7,434 nucleotides long and exhibits a genetic organization characteristic of type b and d oncoviruses. enzootic nasal tumor virus is closely related to the jaagsiekte sheep retrovirus and to sheep endogenous retroviruses.199910196294
jaagsiekte retrovirus is widely distributed both in t and b lymphocytes and in mononuclear phagocytes of sheep with naturally and experimentally acquired pulmonary adenomatosis.jaagsiekte sheep retrovirus (jsrv) is a type d retrovirus specifically associated with a contagious lung tumor of sheep, sheep pulmonary adenomatosis (spa). jsrv replicates actively in the transformed epithelial cells of the lung, and jsrv dna and rna have been detected in lymphoid tissues of naturally affected animals. to determine the lymphoid target cells of jsrv, cd4(+) t cells, cd8(+) t cells, b lymphocytes, and adherent cell (macrophage/monocyte) populations were isolated from the mediasti ...199910196296
novel endogenous type d retroviral particles expressed at high levels in a scid mouse thymic lymphoma.a xenograft model of the human disease langerhans cell histiocytosis (lch) was investigated with severe combined immunodeficiency (scid) mice. transplantation of human lch biopsy material into scid mice resulted in the generation of mouse tumors resembling lymphomas. a thymoma cell line (thye1m6) was generated from one of these mice and found to display significant levels of mg2+-dependent reverse transcriptase activity. electron microscopy revealed particles with type d retroviral morphology bu ...199910233925
sequence comparison of jsrv with endogenous proviruses: envelope genotypes and a novel orf with similarity to a g-protein-coupled receptor.ovine pulmonary carcinoma, a contagious lung cancer of sheep, is caused by the oncogenic jaagsiekte sheep retrovirus (jsrv) that is closely related to a family of endogenous sheep retroviral sequences (esrvs). by using exogenous virus-specific u3 oligonucleotide primers, the entire jsrv proviral genome or its 3' part was amplified from tumor dna. analysis of these proviral sequences revealed a novel open reading frame (orf) within the pol coding region, designated orf x, which was well conserved ...199910366570
jaagsiekte sheep retrovirus is necessary and sufficient to induce a contagious lung cancer in sheep.sheep pulmonary adenomatosis (spa) is a contagious and experimentally transmissible lung cancer of sheep resembling human bronchiolo-alveolar carcinoma. a type d retrovirus, known as jaagsiekte sheep retrovirus (jsrv), has been associated with the etiology of spa, but its exact role in the induction of the tumor has not been clear due to the lack of (i) a tissue culture system for the propagation of jsrv and (ii) an infectious jsrv molecular clone. to investigate the role of jsrv in the etiology ...199910400795
in vitro infection of ovine cell lines by jaagsiekte sheep retrovirus.sheep pulmonary adenomatosis (spa), also known as jaagsiekte or ovine pulmonary carcinoma, is a contagious lung cancer of sheep, originating from type ii pneumocytes and clara cells. previous studies have implicated a type d retrovirus (jaagsiekte sheep retrovirus [jsrv]) as the causative agent of spa. we recently isolated a proviral clone of jsrv from an animal with a spontaneous case of spa (jsrv(21)) and showed that it harbors an infectious and oncogenic virus. this demonstrated that jsrv is ...199910559321
sheep pulmonary adenomatosis: characterization of two pathological forms associated with jaagsiekte retrovirus.pathological and immunohistochemical studies were performed on the lungs of 10 sheep with lesions of "classical" sheep pulmonary adenomatosis (spa) and six sheep with "atypical" lung tumours. lung tumour samples and other tissues from the same 16 animals were tested for the presence of jaagsiekte retrovirus (jsrv) by a polymerase chain reaction (pcr) that amplified a portion of the u3 long terminal repeat. the differences in the gross appearance of the classical and atypical forms paralleled the ...200010627391
an accessory open reading frame (orf-x) of jaagsiekte sheep retrovirus is conserved between different virus isolates.jaagsiekte sheep retrovirus (jsrv) is the etiological agent of a contagious lung tumour of sheep known as sheep pulmonary adenomatosis (syn: ovine pulmonary carcinoma, jaagsiekte). jsrv exhibits a simple genetic organization, characteristic of the type d and type b retroviruses, with the canonical retroviral sequences gag, pro, pol and env encoding the structural proteins of the virion. an additional open reading frame (orf-x), of approximately 500 bp overlapping pol, is present in the only two ...200010653922
retrovirus vectors bearing jaagsiekte sheep retrovirus env transduce human cells by using a new receptor localized to chromosome 3p21.3.jaagsiekte sheep retrovirus (jsrv) is a type d retrovirus associated with a contagious lung tumor of sheep, ovine pulmonary carcinoma. other than sheep, jsrv is known to infect goats, but there is no evidence of human infection. until now it has not been possible to study the host range for jsrv because of the inability to grow this virus in culture. here we show that the jsrv envelope protein (env) can be used to pseudotype moloney murine leukemia virus (momlv)-based retrovirus vectors and that ...200010775607
the long terminal repeat of jaagsiekte sheep retrovirus is preferentially active in differentiated epithelial cells of the lungs.jaagsiekte sheep retrovirus (jsrv) is the etiologic agent of a contagious bronchioloalveolar carcinoma of sheep known as sheep pulmonary adenomatosis (spa; ovine pulmonary carcinoma). jsrv is unique among retroviruses because it transforms the alveolar type ii cells and the nonciliated bronchiolar cells (clara cells) of the lungs; these cells are where jsrv is specifically expressed in both naturally and experimentally spa-affected sheep. in this study, we investigated the cell specificity of js ...200010846056
molecular cloning and functional analysis of three type d endogenous retroviruses of sheep reveal a different cell tropism from that of the highly related exogenous jaagsiekte sheep retrovirus.integrated into the sheep genome are 15 to 20 copies of type d endogenous loci that are highly related to two exogenous oncogenic viruses, jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv). the exogenous viruses cause infectious neoplasms of the respiratory tract in small ruminants. in this study, we molecularly cloned three intact type d endogenous retroviruses of sheep (enjs56a1, enjs5f16, and enjs59a1; collectively called enjrsvs) and analyzed their genomic structures, ...200010933716
evidence for a protein related immunologically to the jaagsiekte sheep retrovirus in some human lung tumours.human bronchioloalveolar carcinoma (bac) is a lung cancer, morphologically similar to an endemic contagious lung neoplasm of sheep called sheep pulmonary adenomatosis (spa) or jaagsiekte. spa is caused by an exogenous type b/d retrovirus (jaagsiekte sheep retrovirus (jsrv)), which prompted the present study to obtain evidence of a retrovirus in bac. a panel of 249 human lung tumours, 21 nontumour lung lesions, four normal lung tissues, 23 adenocarcinomas from other organs and a cell line express ...200010968511
jaagsiekte sheep retrovirus proviral clone jsrv(js7), derived from the js7 lung tumor cell line, induces ovine pulmonary carcinoma and is integrated into the surfactant protein a gene.ovine pulmonary carcinoma (opc) is a contagious neoplasm of alveolar epithelial type ii (atii) or clara cells caused by a type d/b chimeric retrovirus, jaagsiekte sheep retrovirus (jsrv). here we report the isolation, sequencing, pathogenicity, and integration site of a jsrv provirus isolated from a sheep lung tumor cell line (js7). the sequence of the virus was 93 to 99% identical to other jsrv isolates and contained all of the expected open reading frames. to produce virions and test its infec ...200111287573
candidate tumor suppressor hyal2 is a glycosylphosphatidylinositol (gpi)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation.jaagsiekte sheep retrovirus (jsrv) can induce rapid, multifocal lung cancer, but jsrv is a simple retrovirus having no known oncogenes. here we show that the envelope (env) gene of jsrv has the unusual property that it can induce transformation in rat fibroblasts, and thus is likely to be responsible for oncogenesis in animals. retrovirus entry into cells is mediated by env interaction with particular cell-surface receptors, and we have used phenotypic screening of radiation hybrid cell lines to ...200111296287
direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus dna.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary carcinoma, a unique animal model for human bronchioalveolar carcinoma. we previously isolated a jsrv proviral clone and showed that it was both infectious and oncogenic. thus jsrv is necessary and sufficient for the development of ovine pulmonary carcinoma, but no data are available on the mechanisms of transformation. inspection of the jsrv genome reveals standard retroviral genes, but no evidence for a viral oncogene. ...200111296288
jaagsiekte sheep retrovirus can be detected in the peripheral blood during the pre-clinical period of sheep pulmonary adenomatosis.peripheral blood leukocytes (pbls) and tissue samples from 36 sheep were examined for jaagsiekte sheep retrovirus (jsrv) by hemi-nested pcr. animals were classified according to the status of sheep pulmonary adenomatosis (spa), which was confirmed by pathological examination, as follows: (i) sheep with classical spa (cspa, n=10), (ii) sheep with atypical spa (aspa, n=6), (iii) non-affected sheep from spa-affected flocks (in-contact, n=10) and (iv) non-affected sheep from spa-free flocks (control ...200111369879
jaagsiekte sheep retrovirus env protein stabilizes retrovirus vectors against inactivation by lung surfactant, centrifugation, and freeze-thaw cycling.jaagsiekte sheep retrovirus (jsrv) replicates in the lungs of sheep and causes the secretion of copious lung fluid containing the virus. adaptation of jsrv to infection and replication in the lung and its apparent resistance to the denaturing activity of lung fluid suggest that vectors based on jsrv would be useful for gene therapy targeted to the lung. we show here that a retrovirus vector bearing the jsrv env is stable during treatment with lung surfactant while an otherwise identical vector b ...200111507233
association of jaagsiekte sheep retrovirus with pulmonary carcinoma in sardinian moufflon (ovis musimon).bronchiolo-alveolar carcinoma has been described in man and in several animal species, including cattle, dogs, opossums, goats and sheep. in sheep, a bronchiolo-alveolar carcinoma, known as ovine pulmonary carcinoma (opc), is caused by jaagsiekte sheep retrovirus (jsrv), an exogenous type d retrovirus. in the mid-1980s, a severe outbreak of a disease resembling opc was described in captive sardinian moufflon (ovis musimon). in the present study, the use of polymerase chain reaction (pcr) amplifi ...200111578130
a phosphatidylinositol 3-kinase docking site in the cytoplasmic tail of the jaagsiekte sheep retrovirus transmembrane protein is essential for envelope-induced transformation of nih 3t3 cells.jaagsiekte sheep retrovirus (jsrv) is the causative agent of a transmissible lung cancer of sheep known as ovine pulmonary carcinoma. recently, we have found that the expression of the jsrv envelope (env) is sufficient to transform mouse nih 3t3 cells in classical transformation assays. to further investigate the mechanisms of jsrv oncogenesis, we generated a series of envelope chimeras between jsrv and the jsrv-related endogenous retroviruses of sheep (enjsrvs) and assessed them in transformati ...200111602740
absence of jaagsiekte sheep retrovirus dna and rna in bronchioloalveolar and conventional human pulmonary adenocarcinoma by pcr and rt-pcr analysis.bronchioloalveolar adenocarcinoma (bac) morphologically resembles sheep pulmonary adenomatosis (spa), a contagious ovine pulmonary adenocarcinoma caused by the jaagsiekte sheep retrovirus (jsrv). previously, positivity for jsrv by immunostaining, reverse-transcription polymerase chain reaction (rt-pcr), and western blot was reported in most nonmucinous bacs. our objective in this study was to analyze additional bac subtypes and conventional adenocarcinomas (ca) to further substantiate this assoc ...200111679936
expression of endogenous betaretroviruses in the ovine uterus: effects of neonatal age, estrous cycle, pregnancy, and progesterone.the ovine genome contains 15 to 20 copies of endogenous retroviruses (enjsrvs) highly related to the oncogenic jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus. enjsrvs are highly expressed in the endometrial lumenal epithelia (le) and glandular epithelia (ge) of the ovine uterus. the effects of neonatal age, estrous cycle, pregnancy, and progesterone on expression of enjsrvs in the ovine uterus were determined. expression of enjsrv rnas was absent from the uterus of ewes at bir ...200111689612
retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer.studies on the molecular mechanisms of transformation of retrovirus-induced neoplasms in domestic and laboratory animal species have provided insights into the genetic basis of cancer. ovine pulmonary adenocarcinoma (opa) is a retrovirus-induced spontaneous lung tumor of sheep that has striking analogies to some forms of human adenocarcinoma. the etiologic agent of opa, jaagsiekte sheep retrovirus (jsrv), is unique among retroviruses for having a specific tropism for the differentiated epithelia ...200111698564
mechanism of cell entry and transformation by enzootic nasal tumor virus.enzootic nasal tumor virus (entv) induces nasal epithelial cancer in infected sheep, but it is a simple retrovirus lacking a known oncogene. entv is closely related to jaagsiekte sheep retrovirus (jsrv), which also causes cancer in sheep but in the epithelial cells of the lower airways and alveoli. here we show that as with jsrv, the envelope (env) protein of entv can transform cultured cells and thus is likely to be responsible for oncogenesis in animals. in addition, the entv env protein media ...200211836391
hnf-3beta is a critical factor for the expression of the jaagsiekte sheep retrovirus long terminal repeat in type ii pneumocytes but not in clara cells.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa), a sheep lung cancer that resembles human lung adenocarcinoma or bronchioloaveolar carcinoma (bac). jsrv is the only retrovirus that shows lung tropism and induces pulmonary carcinoma. several lines of evidence suggest that the lung tropism for jsrv is mainly determined by the viral long terminal repeats (ltr). in a previous study, we showed that hnf-3alpha and -3beta were able to transactivate the ...200211878911
spliced and prematurely polyadenylated jaagsiekte sheep retrovirus-specific rnas from infected or transfected cells.jaagsiekte sheep retrovirus (jsrv) is the etiologic agent of a contagious lung cancer of sheep, ovine pulmonary adenocarcinoma (opa). in this study, we characterized the virus-specific rnas in 293t cells transiently transfected with a human cytomegalovirus promoter-driven jsrv expression plasmid, in productively infected ohh1.lu deer lung cells, and in opa tumors from field isolates. typical unspliced (presumably for gag, pro, and pol) and singly spliced env mrnas were detected. in addition, six ...200211886276
envelope-induced cell transformation by ovine betaretroviruses.ovine betaretroviruses include jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv). jsrv and entv represent a unique class of oncogenic retroviruses that induce tumors of the respiratory tract. jsrv and entv are highly related but induce different diseases. expression of the jsrv envelope (env) induces transformation of rodent fibroblasts in vitro and phosphorylation of akt, a central player in the phosphatidylinositol 3-kinase (pi-3k)/akt signal transduction pathway. howeve ...200211991967
alveolar type ii cells expressing jaagsiekte sheep retrovirus capsid protein and surfactant proteins are the predominant neoplastic cell type in ovine pulmonary adenocarcinoma.ovine pulmonary adenocarcinoma is caused by jaagsiekte sheep retrovirus. to gain insight into the histogenesis and viral pathogenesis of this neoplasm, the tumor cell phenotypes and differentiation state were correlated with the distribution of jaagsiekte sheep retrovirus capsid protein in neoplastic and normal cells of the lung in nine naturally occurring and 12 experimentally induced cases of ovine pulmonary adenocarcinoma. overall, 82% of tumor cells had ultrastructural features consistent wi ...200212014498
systemic immune responses following infection with jaagsiekte sheep retrovirus and in the terminal stages of ovine pulmonary adenocarcinoma.jaagsiekte sheep retrovirus (jsrv) is the aetiological agent of ovine pulmonary adenocarcinoma (opa). to monitor changes in cellular immune function during jsrv infection, lymphoproliferation in response to various mitogens was measured in the blood of conventionally housed and specific-pathogen-free lambs experimentally infected with jsrv until the development of opa and compared with uninfected control lambs. in addition, blood samples collected from adult field cases in the terminal stages of ...200212075095
comparative oncological studies of feline bronchioloalveolar lung carcinoma, its derived cell line and xenograft.although certain neoplasms are unique to man, others occur across species. one such neoplasm is bronchioloalveolar lung carcinoma (bac), a neoplasm of the type ii pneumocyte that affects humans, sheep, and small animals (dogs and cats). human bac occurs largely in nonsmokers. sheep bac is caused by the jaagsiekte retrovirus and is endemic and contagious. feline bac is neither endemic nor contagious and occurs sporadically and spontaneously in older purebred cats. in these respects, feline bac is ...200212097296
lack of dna evidence for jaagsiekte sheep retrovirus in human bronchioloalveolar carcinoma. 200212152170
the jaagsiekte sheep retrovirus envelope gene induces transformation of the avian fibroblast cell line df-1 but does not require a conserved sh2 binding domain.ovine pulmonary adenocarcinoma, caused by jaagsiekte sheep retrovirus (jsrv), is a naturally occurring retrovirus-induced pulmonary neoplasm of sheep. we report here that expression of the jsrv env gene is sufficient to transform an avian embryo fibroblast cell line, df-1. df-1 cells transfected with an avian sarcoma-leukaemia retroviral expression vector containing the jsrv env gene [prcasbp(a)-j:env] exhibited changes consistent with transformation, including contraction and rounding of cells ...200212388809
endogenous jaagsiekte sheep retrovirus rna is expressed by different cell types in ovine foetus and placenta.the endogenous retroviruses are inherited elements transmitted trough the germline of most animal species and their biological role is still controversial. ovine pulmonary carcinoma (opc) represents a good model for studying the interactions of endogenous retroviruses with their exogenous counterparts. the type d exogenous retrovirus known as jaagsiekte sheep retro-virus (jsrv) is necessary and sufficient to cause opc in domestic and wild sheep, but both affected and unaffected animals host in t ...200212472123
receptor usage and fetal expression of ovine endogenous betaretroviruses: implications for coevolution of endogenous and exogenous retroviruses.betaretroviruses of sheep include two exogenous viruses, jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv), and a group of endogenous viruses known as enjsrvs. the exogenous jsrv and entv are the etiological agents of ovine pulmonary adenocarcinoma (opa) and enzootic nasal tumor (ent), respectively. sheep affected by opa or ent do not show an appreciable antibody response to jsrv or entv. consequently, it is conceivable that enjsrv expression in the fetal lamb tolerizes sh ...200312477881
role of virus receptor hyal2 in oncogenic transformation of rodent fibroblasts by sheep betaretrovirus env proteins.the ovine betaretroviruses jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv) cause contagious cancers in the lungs and upper airways of sheep and goats. oncogenic transformation assays using mouse and rat fibroblasts have localized the transforming activity to the env proteins encoded by these viruses, which require the putative lung and breast cancer tumor suppressor hyaluronidase 2 (hyal2) to promote virus entry into cells. these results suggested the hypothesis that the ...200312584308
a history of ovine pulmonary adenocarcinoma (jaagsiekte) and experiments leading to the deduction of the jsrv nucleotide sequence.jaagsiekte (js), a contagious cancer affecting the lungs of sheep has been called many names over the years. at a recent workshop in missilac, france it was agreed that the disease would be called ovine pulmonary adenocarcinoma (opa). the disease is caused by an infectious retrovirus called jaagsiekte sheep retrovirus (jsrv). this chapter focuses on the early research that led up to the isolation, cloning and sequencing of the exogenous infectious form of jsrv and the demonstration that it has a ...200312596893
pathology of ovine pulmonary adenocarcinoma.clinical, gross pathology, histopathology and electron microscopy of the ovine pulmonary adenocarcinoma (opa, jaagsiekte) either natural or experimentally induced in sheep, goat and moufflon are described. opa is caused by an oncogenic betaretrovirus,jaagsiekte sheep retrovirus (jsrv). most natural cases of opa appear in animals 1-4 years old. there is no evidence of sex or breed susceptibility. sheep affected by opa show an afebrile respiratory illness associated with loss of weight. a very cha ...200312596894
natural history of jsrv in sheep.ovine pulmonary adenocarcinoma (opa) is a contagious lung tumour of sheep and, rarely, goats that arises from two types of secretory epithelial cell that retain their luxury function of surfactant synthesis and secretion. it is classified as a low-grade adenocarcinoma and is viewed as a good model for epithelial neoplasia because of its morphological resemblance to the human lung tumour, bronchioloalveolar adenocarcinoma. opa is present in most of the sheep rearing areas of the globe and, in aff ...200312596895
molecular biology of jaagsiekte sheep retrovirus.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa), a contagious lung cancer of sheep. until recently, research on jsrv/opa was hampered by the lack of a tissue culture system for the propagation of the virus. historically, pathological samples (lung fluid) collected from sheep affected by opa were the only source of infectious jsrv. thus studies on the jsrv/opa system were conducted only where field isolates of opa cases were readily available. in ...200312596896
endogenous retroviruses related to jaagsiekte sheep retrovirus.ovine betaretroviruses consist of exogenous viruses [jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus, (entv)] associated with neoplastic diseases of the respiratory tract and 15-20 endogenous viruses (enjsrv) stably integrated in the ovine and caprine genome. phylogenetic analysis of this group of retroviruses suggests that the enjsrv can be considered as 'modern' endogenous retroviruses with active, exogenous counterparts. sequence analysis of jsrv, entv and enjsrv suggests th ...200312596897
transformation and oncogenesis by jaagsiekte sheep retrovirus.jaagsiekte sheep retrovirus (jsrv) is an exogenous retrovirus of sheep that induces a contagious lung cancer, ovine pulmonary adenocarcinoma (opa). jsrv is a potent carcinogen in the experimental setting, inducing end-stage tumors at around 6 weeks of age when newborn lambs are inoculated intratracheally. despite this rapid oncogenesis, inspection of the jsrv genome sequence does not reveal any obvious viral oncogenes. in this review, recent advances in studies of jsrv oncogenic transformation a ...200312596898
identification of hyal2 as the cell-surface receptor for jaagsiekte sheep retrovirus and ovine nasal adenocarcinoma virus.jaagsiekte sheep retrovirus (jsrv) and ovine nasal adenocarcinoma virus (onav) replicate in the airway and cause epithelial cell tumors through the activity of their envelope (env) proteins. identification of the receptor(s) that mediate cell entry by these viruses is crucial to understanding the oncogenic activity of env and for the development of gene therapy vectors based on these viruses that are capable of targeting airway cells. to identify the viral receptor(s) and to further study the bi ...200312596899
enzootic nasal adenocarcinoma of sheep and goats.enzootic nasal adenocarcinoma is a contagious tumour of the mucosal nasal glands affecting young adult sheep or goats. the disease occurs naturally in all continents except australia and new zealand. clinical signs include continuous nasal discharge, respiratory distress, exophthalmos and skull deformations. the tumour is classified histologically as a low-grade adenocarcinoma. nasal glands of both respiratory and olfactory muosal glands seem to be the origin of the neoplasia. it has been experi ...200312596900
pathology of human bronchioloalveolar carcinoma and its relationship to the ovine disease.lung cancer is a leading cause of cancer with a poor prognosis. bronchioloalveolar carcinoma (bac) is a rare tumor that has always intrigued physicians. since the last world health organization classification the pathology has been clarified; bac per se is an adenocarcinoma with a pure bronchioloalveolar growth pattern and appears as an in situ alveolar adenocarcinoma. more usually bac is a clinically recognizable entity presenting as multi-focal nodules evolving towards pneumonia associated wit ...200312596901
hyaluronidase 2 negatively regulates ron receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus.the candidate tumor-suppressor gene hyaluronidase 2 (hyal2) encodes a glycosylphosphatidylinositol-anchored cell-surface protein that serves as an entry receptor for jaagsiekte sheep retrovirus, a virus that causes contagious lung cancer in sheep that is morphologically similar to human bronchioloalveolar carcinoma. the viral envelope (env) protein alone can transform cultured cells, and we hypothesized that env could bind and sequester the hyal2 receptor and thus liberate a potential oncogenic ...200312676986
transformation of rodent fibroblasts by the jaagsiekte sheep retrovirus envelope is receptor independent and does not require the surface domain.jaagsiekte sheep retrovirus (jsrv) is the etiological agent of a contagious lung cancer of sheep known as ovine pulmonary adenocarcinoma (opa). expression of the jsrv envelope protein (env) is sufficient to transform immortalized and primary fibroblasts, but the precise mechanisms of this process are not known. the cellular receptor for jsrv is hyaluronidase 2 (hyal-2), the product of a putative tumor suppressor gene that in humans maps to a chromosomal region frequently deleted in the developme ...200312743291
putative phosphatidylinositol 3-kinase (pi3k) binding motifs in ovine betaretrovirus env proteins are not essential for rodent fibroblast transformation and pi3k/akt activation.jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv) are simple betaretroviruses that cause epithelial cell tumors in the lower and upper airways of sheep and goats. the envelope (env) glycoproteins of both viruses can transform rodent and chicken fibroblasts, indicating that they play an essential role in oncogenesis. previous studies found that a yxxm motif in the env cytoplasmic tail, a putative docking site for phosphatidylinositol 3-kinase (pi3k) after tyrosine phosphory ...200312829832
characterization of enzootic nasal tumour virus of goats: complete sequence and tissue distribution.the complete genome sequence of a new isolate of enzootic nasal tumour virus (entv-2), associated with enzootic nasal adenocarcinoma (ena) of goats, was determined. the genome exhibits a genetic organization characteristic of beta-retroviruses. entv-2 is closely related to the retrovirus (entv-1) associated with enzootic adenocarcinoma of sheep, and to jaagsiekte retrovirus. the main sequence differences between these viruses reside in orfx, the u3 ltr, two small regions in gag and the transmemb ...200312867657
relevance of akt phosphorylation in cell transformation induced by jaagsiekte sheep retrovirus.expression of the jsrv envelope (env) is sufficient to transform immortalized rodent fibroblasts. a putative docking site for the pi3-k kinase (y(590)-x-x-m(593)) in the cytoplasmic tail of the transmembrane domain of the jsrv env is a major determinant of viral-induced cell transformation. akt is constitutively phosphorylated in rodent fibroblasts transformed by the jsrv env. however, recent data suggest that y590 and m593 are not necessary for jsrv env-induced transformation of the immortalize ...200312890624
chromosomal distribution of endogenous jaagsiekte sheep retrovirus proviral sequences in the sheep genome.a family of endogenous retroviruses (enjsrv) closely related to jaagsiekte sheep retrovirus (jsrv) is ubiquitous in domestic and wild sheep and goats. southern blot hybridization studies indicate that there is little active replication or movement of the enjsrv proviruses in these species. two approaches were used to investigate the distribution of proviral loci in the sheep genome. fluorescence in situ hybridization (fish) to metaphase chromosome spreads using viral dna probes was used to detec ...200312915578
transformation of mouse fibroblasts by jaagsiekte sheep retrovirus envelope does not require phosphatidylinositol 3-kinase.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma, a transmissible lung cancer of sheep. the envelope of jsrv may have oncogenic properties, since it can morphologically transform mouse nih 3t3 cells and other fibroblast lines. recently, we found that the cytoplasmic tail of the envelope transmembrane (tm) protein is necessary for transformation, and in particular a consensus binding motif (yxxm) for phosphatidylinositol 3-kinase (pi3k) is important. mor ...200312941905
endogenous betaretroviruses of sheep: teaching new lessons in retroviral interference and adaptation.the endogenous betaretroviruses of small ruminants offer an excellent model to investigate the biological relevance of endogenous retroviruses (ervs). approximately twenty copies of endogenous betaretroviruses (enjsrvs) are present in the genome of sheep and goats. enjsrvs are highly related to jaagsiekte sheep retrovirus (jsrv) and the enzootic nasal tumour virus (entv), the causative agents of naturally occurring carcinomas of the respiratory tract of sheep. enjsrvs interact/interfere at diffe ...200414718613
jaagsiekte sheep retrovirus envelope efficiently pseudotypes human immunodeficiency virus type 1-based lentiviral vectors.jaagsiekte sheep retrovirus (jsrv) infects lung epithelial cells in sheep, and oncoretroviral vectors bearing jsrv env can mediate transduction of human cells, suggesting that such vectors might be useful for lung-directed gene therapy. here we show that jsrv env can also efficiently pseudotype a human immunodeficiency virus type 1-based lentiviral vector, a more suitable vector for transduction of slowly dividing lung epithelial cells. we created several chimeric env proteins that, unlike the p ...200414963173
cd208/dendritic cell-lysosomal associated membrane protein is a marker of normal and transformed type ii pneumocytes.dendritic cell-lysosomal associated membrane protein (dc-lamp)/cd208, a member of the lysosomal associated membrane protein (lamp) family, is specifically expressed by human dcs on activation. however, its mouse counterpart could not be detected in mature dcs. the present study demonstrates that dc-lamp is constitutively expressed by mouse, sheep, and human type ii pneumocytes. confocal and immunoelectron microscopy showed that mouse dc-lamp protein co-localizes with lbm180, a specific marker fo ...200414982840
ovine pulmonary adenomatosis in patagonia, argentina.an outbreak of pulmonary adenomatosis (opa) occurred in sheep in patagonia, argentina's southernmost region. on the affected farm, nine animals died over a 6-month period with pulmonary lesions of opa. in all cases, the histology of the lungs was characterized by proliferation of cuboideal and prismatic cells lining the alveoli. inflammatory exudates and accumulation of alveolar macrophages were marked in most cases, but in six of the cases there was no excess fluid in the airways. the presence ...200414992245
retrovirus-induced lung cancer: mechanisms of transformation of alveolar type ii epithelial cells. 200415136444
late viral interference induced by transdominant gag of an endogenous retrovirus.the sheep genome harbors approximately 20 copies of endogenous retroviruses (enjsrvs) closely related to the exogenous and oncogenic jaagsiekte sheep retrovirus (jsrv). one of the enjsrv loci, enjs56a1, has a defect for viral exit. we report a previously uncharacterized mechanism of retroviral interference. the defect possessed by enjs56a1 is determined by its gag protein and is transdominant over the exogenous jsrv. by electron microscopy, cells transfected by enjs56a1, with or without jsrv, sh ...200415263098
analysis of integration sites of jaagsiekte sheep retrovirus in ovine pulmonary adenocarcinoma.ovine pulmonary adenocarcinoma (opa) is an infectious lung tumor of sheep caused by jaagsiekte sheep retrovirus (jsrv). to test the hypothesis that jsrv insertional mutagenesis is involved in the oncogenesis of opa, we cloned and characterized 70 independent integration sites from 23 cases of opa. multiple integration sites were identified in most tumors. blast analysis of the sequences did not disclose any potential oncogenic motifs or any identical integration sites in different tumors. thirty ...200415280459
detection and characterization of betaretroviral sequences, related to sheep jaagsiekte virus, in africans from nigeria and cameroon.jaagsiekte retrovirus (jsrv) causes ovine pulmonary adenomatosis (opa) that resembles bronchioloalveolar carcinoma (bac) in humans. to test the possible role of jsrv in human diseases, dna specimens from 103 individuals either healthy or suffering from lung carcinomas were analyzed for jsrv sequences. orf-x sequences were detected in 19 of 64 samples and gag-prt sequences in 4 of 38 samples, predominantly in individuals from africa. sequences obtained from orf-x amplimers varied in-between each ...200415351203
transformation and scattering activities of the receptor tyrosine kinase ron/stk in rodent fibroblasts and lack of regulation by the jaagsiekte sheep retrovirus receptor, hyal2.the envelope (env) protein of jaagsiekte sheep retrovirus (jsrv) can transform cells in culture and is likely to be the main factor responsible for lung cancer induction by jsrv in animals. a recent report indicates that the epithelial-cell transforming activity of jsrv env depends on activation of the cell-surface receptor tyrosine kinase mst1r (called ron for the human and stk for the rodent orthologs). in the immortalized line of human epithelial cells used (beas-2b cells), the virus receptor ...200415363108
multiple domains of the jaagsiekte sheep retrovirus envelope protein are required for transformation of rodent fibroblasts.jaagsiekte sheep retrovirus (jsrv) is an exogenous retrovirus of sheep that induces a contagious lung cancer, ovine pulmonary adenocarcinoma. we previously showed that the gene encoding jsrv envelope protein (env) appears to function as an oncogene, since it can transform mouse nih 3t3 cells. the cytoplasmic tail of the env transmembrane protein (tm) is necessary for the transformation. however, previous experiments did not exclude the involvement of the env surface protein (su) in transformatio ...200415367614
successful induction of ovine pulmonary adenocarcinoma in lambs of different ages and detection of viraemia during the preclinical period.ovine pulmonary adenocarcinoma (opa) can be reproduced consistently in neonatal lambs by intratracheal injection of inocula containing jaagsiekte sheep retrovirus (jsrv). in this study, clinical disease, confirmed pathologically as opa, was induced in a high proportion of lambs that had been inoculated intratracheally with infectious lung fluid at 1, 3 and 6 months of age. the incubation periods, however, were longer in these three age groups than in 1-week-old lambs that were used as controls. ...200415483246
coexistence of enzootic nasal adenocarcinoma and jaagsiekte retrovirus infection in sheep.ten sheep naturally affected with enzootic nasal adenocarcinoma (ena), a disease associated with ovine enzootic nasal tumour virus (entv-1), were found also to be infected with jaagsiekte sheep retrovirus (jsrv), the causal agent of ovine pulmonary adenocarcinoma (opa). only one of the sheep showed opa lung lesions. the animals belonged to 10 flocks located in a geographical area in which opa is frequently seen. entv-1 was found in all the ena tumours but only occasionally in extra-tumoral sites ...200415511533
expression and characterization of a soluble, active form of the jaagsiekte sheep retrovirus receptor, hyal2.retrovirus entry into cells is mediated by specific interactions between virus envelope glycoproteins and cell surface receptors. many of these receptors contain multiple membrane-spanning regions, making their purification and study difficult. the jaagsiekte sheep retrovirus (jsrv) receptor, hyaluronidase 2 (hyal2), is a glycosylphosphatidylinositol (gpi)-anchored molecule containing no peptide transmembrane regions, making it an attractive candidate for study of retrovirus entry. further, the ...200515596803
improved enzootic nasal tumor virus pseudotype packaging cell lines reveal virus entry requirements in addition to the primary receptor hyal2.enzootic nasal tumor virus (entv) and jaagsiekte sheep retrovirus (jsrv) are closely related retroviruses that cause epithelial cancers of the respiratory tract in sheep and goats. both viruses use the glycosylphosphatidylinositol (gpi)-anchored cell surface protein hyaluronidase 2 (hyal2) as a receptor for cell entry, and entry is mediated by the envelope (env) proteins encoded by these viruses. retroviral vectors bearing jsrv env can transduce cells from a wide range of species, with the excep ...200515596804
transformation of madin-darby canine kidney epithelial cells by sheep retrovirus envelope proteins.jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv) induce epithelial tumors in the airways of sheep and goats. in both of these simple retroviruses, the envelope (env) protein is the active oncogene. furthermore, jsrv env can transform cultured cells by two distinct mechanisms. in rat and mouse fibroblasts, the cytoplasmic tail of jsrv env is essential for transformation, which involves activation of the phosphatidylinositol 3-kinase (pi3k)/akt pathway, and the virus recept ...200515613321
inclusion of jaagsiekte sheep retrovirus proviral elements markedly increases lentivirus vector pseudotyping efficiency.retroviral pseudotyping for gene transfer applications endeavors to alter vector tropism and maintain a suitable titer. we investigated the compatibility of the jaagsiekte sheep retrovirus (jsrv) envelope glycoprotein with the feline immunodeficiency virus (fiv) vector. a construct consisting of the minimal jsrv env coding region expressed from a standard mammalian expression plasmid generated fiv vector titers of approximately 10(4) tu/ml following standard triple transfection, collection of su ...200515727943
variable regions 1 and 2 (vr1 and vr2) in jsrv gag are not responsible for the endogenous jsrv particle release defect.jaagsiekte sheep retrovirus (jsrv) is a betaretrovirus causing ovine pulmonary adenocarcinoma, a transmissible lung tumor of sheep. a very closely related endogenous retrovirus (enjsrv) occurs as 15 to 20 copies in the genome of all sheep, and is not known to be linked to pathogenesis. we previously localized a particle release defect of the full-length endogenous-derived expression construct pcmv2enjs56a1 to the amino-terminal region of gag that incorporates the two variable regions vr1 and vr2 ...200515744563
roles of the ras-mek-mitogen-activated protein kinase and phosphatidylinositol 3-kinase-akt-mtor pathways in jaagsiekte sheep retrovirus-induced transformation of rodent fibroblast and epithelial cell lines.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma (opa), a transmissible lung cancer of sheep. the virus can induce tumors rapidly, and we previously found that the jsrv envelope protein (env) functions as an oncogene, because it can transform mammalian and avian fibroblast cell lines. (n. maeda, proc. natl. acad. sci. usa 98:4449-4454, 2001). the molecular mechanisms of jsrv env transformation are of considerable interest. several reports suggested that ...200515767444
effects on the serotoninergic system in sub-acute transmissible spongiform encephalopathies: current data, hypotheses, suggestions for experimentation.sub-acute transmissible spongiform encephalopathies (tses), or prion diseases, are affections in which little is known of their etiology. the predominant theory stipulates that an abnormal protease-resistant prion protein (prpres) would be infectious by directly inducing its defective conformation to the normal native protein (prpc). the function of prpc remains unknown. the preferred localization of prpc at the level of the synapses supposes a function in neuronal transmission. several neurotra ...200515780484
sheep endogenous betaretroviruses (enjsrvs) and the hyaluronidase 2 (hyal2) receptor in the ovine uterus and conceptus.the ovine genome contains approximately 20 copies of endogenous betaretroviruses (enjsrvs) that are highly related to two exogenous oncogenic viruses, jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus. the cellular receptor for both jsrv and the enjsrvs is hyaluronidase 2 (hyal2). in this study, we assessed expression of enjsrvs envelope (env) and hyal2 mrnas in the ovine uterus and conceptus (embryo/fetus and extraembryonic membranes) throughout gestation. by reverse transcripti ...200515788753
sheep retrovirus structural protein induces lung tumours.jaagsiekte sheep retrovirus (jsrv) causes a contagious lung cancer in sheep and goats, with significant animal health and economic consequences. the host range of jsrv is in part limited by species-specific differences in the virus entry receptor, hyaluronidase 2 (hyal2), which is not functional as a receptor in mice but is functional in humans. sheep are immunotolerant of jsrv because of the expression of closely related endogenous retroviruses, which are not present in humans and most other sp ...200515829964
gene transfer to respiratory epithelia with lentivirus pseudotyped with jaagsiekte sheep retrovirus envelope glycoprotein.a feline immunodeficiency virus (fiv)-based lentiviral vector was pseudotyped to identify envelope (env) glycoproteins that direct efficient gene transfer to pulmonary epithelia for the treatment or prevention of lung diseases. the envelope glycoprotein from the jaagsiekte sheep retrovirus (jsrv) is a candidate under investigation. we utilized high titer fiv vector (>10(8) tu/ml) pseudotyped with the jsrv env glycoprotein (jsrvfiv) to study the transduction of polarized primary cultures of human ...200515871679
an influx of macrophages is the predominant local immune response in ovine pulmonary adenocarcinoma.infection with a retrovirus, jaagsiekte sheep retrovirus (jsrv), causes ovine pulmonary adenocarcinoma (opa). the excess production of surfactant proteins by alveolar tumour cells results in increased production of pulmonary fluid, which is characteristically expelled through the nostrils of affected sheep. the immune response to jsrv and the tumour is poorly understood: no jsrv-specific circulating antibodies or t cells have been detected to date. the aim of the present study was to obtain phen ...200515878202
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
a pcr technique for the detection of jaagsiekte sheep retrovirus in the blood suitable for the screening of ovine pulmonary adenocarcinoma in field conditions.ovine pulmonary adenocarcinoma (opa) is a naturally occurring contagious lung neoplasia caused by jaagsiekte sheep retrovirus (jsrv). although no specific circulating antibodies against the virus can be detected in infected sheep, jsrv proviral dna sequences can be found in peripheral blood leukocytes (pbls) in clinically affected and in a proportion of in contact animals. in this study, existing hemi-nested pcr procedure is compared with a new one-step pcr technique that was developed to minimi ...200516054897
a moloney murine leukemia virus driven by the jaagsiekte sheep retrovirus enhancers shows enhanced specificity for infectivity in lung epithelial cells.jaagsiekte sheep retrovirus (jsrv) is the etiologic agent of ovine pulmonary adenocarcinoma (opa), a transmissible lung cancer in sheep. one of the unique features of this virus is that in infected animals, the only tissues that show expression of the virus are the tumor cells in the lung. we previously showed that the jsrv long terminal repeat (ltr) is preferentially active in murine lung epithelial cell lines (mle-15 and mtcc1-2). to further explore the tissue specificity, we inserted the jsrv ...200516175331
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
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
in vivo and in vitro analysis of factor binding sites in jaagsiekte sheep retrovirus long terminal repeat enhancer sequences: roles of hnf-3, nf-i, and c/ebp for activity in lung epithelial cells.jaagsiekte sheep retrovirus (jsrv) is the causative agent of ovine pulmonary adenocarcinoma, a contagious lung cancer of sheep that arises from type ii pneumocytes and clara cells of the lung epithelium. studies of the tropism of this virus have been hindered by the lack of an efficient system for viral replication in tissue culture. to map regulatory regions important for transcriptional activation, an in vivo footprinting method that couples dimethyl sulfate treatment and ligation-mediated pcr ...200616352558
telomerase activation in a model of lung adenocarcinoma.ovine pulmonary adenocarcinoma (opa) is a lung cancer strikingly similar to the pneumonic-type mixed invasive adenocarcinoma with a predominant bronchioloalveolar component in humans. telomerase activity in opa and the potential involvement of the kinase akt in telomerase activation and regulation of cell proliferation were investigated. lung tissues were collected from sheep with a histopathological diagnosis of opa or controls. epithelial cell cultures were derived in vitro from lung tissues. ...200616455826
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