characterization of enzootic nasal tumor virus capsid antigen.the rt-pcr was carried out on tumor tissue from sheep with enzootic nasal tumor (ent), using primers designed from conserved amino acid regions of related type d retroviruses. a 591 bp pcr fragment, corresponding to 90% of the capsid antigen was cloned, sequenced and expressed in e. coli. alignment with ovine pulmonary carcinoma (opc) virus showed 93% nucleotide and 96% amino acid homology. no amplification occurred when dna from ovine fetal cell line was used as template. the recombinant protei ...19969008337
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
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
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
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
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
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
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
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
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
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
[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
full-length genome sequence analysis of enzootic nasal tumor virus reveals an unusually high degree of genetic stability.enzootic nasal tumor virus (entv) is a betaretrovirus of sheep (entv-1) and goats (entv-2) associated with neoplastic transformation of epithelial cells of the ethmoid turbinate. confirmation of the role of entv in the pathogenesis of enzootic nasal adenocarcinoma (ena) has yet to be resolved due to the lack of an infectious molecular clone and the inability to culture the virus. very little is known about the prevalence of this disease, particularly in north america, and only one full-length se ...201020398709
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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