Enzootic Nasal Adenocarcinoma of Sheep and Goats

Heras, M. De las; Ortı́n, A.; Cousens, Chris; Minguijón, E.; Sharp, J. M.

doi:10.1007/978-3-642-55638-8_8

Cited by 62 publications

(84 citation statements)

References 25 publications

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“…OPA is a tumour derived from type II pneumocytes and Clara cells in the lung, whereas ENA arises from secretory epithelial cells of the ethmoid turbinate. The gross pathology and histology of ENA in sheep and goats appear to be identical (De las Heras et al, 2003). The association between ENA and enzootic nasal tumour virus (ENTV) is well established (Cousens et al, , 1999De las Heras et al, 1991a, b, 1993Vitelozzi et al, 1993), although less well characterized than the relationship between OPA and jaagsiekte sheep retrovirus (JSRV) (Palmarini et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…The close homology between JSRV, ENTV and ovERVs was a problem for the development of specific detection techniques for these viruses, but this was resolved by the identification of small areas of sequence that differ between them (Bai et al, 1996;Palmarini et al, 1996;Cousens et al, 1996Cousens et al, , 1999. The suggestion that ENTV of sheep and ENTV of goats are distinct viruses (De las Heras et al, 2003) led us to undertake the complete sequencing of a goat ENTV isolate, named ENTV-2, using samples from a single ENA-affected goat. Here we present the sequence of the complete genome of ENTV-2, an exogenous retrovirus with a genetic organization characteristic of b-retroviruses.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of enzootic nasal tumour virus of goats: complete sequence and tissue distribution

Ortı́n

Cousens

Minguijón

et al. 2003

Journal of General Virology

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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 b-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 transmembrane (TM) region of env. Sequence analysis of the TM region of env from several sheep and goats naturally affected by ENA suggested that ENTV-1 and ENTV-2 are distinct viruses rather than geographical variants. Although both viruses transform secretory epithelial cells of the ethmoid turbinate, the study of their tissue distribution using specific PCRs showed that ENTV-2 establishes a disseminated lymphoid infection whereas ENTV-1 is mainly confined to the tumour.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of enzootic nasal tumour virus of goats: complete sequence and tissue distribution

Ortı́n

Cousens

Minguijón

et al. 2003

Journal of General Virology

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“…Enzootic nasal adenocarcinomas of sheep and goats originate from the ethmoid turbinates and show a rising prevalence worldwide (De las Heras et al, 2003;Fox et al, 2011). This tumour is invasive, mainly of low grade, and it rarely forms metastases (De las Heras et al, 1991Heras et al, , 2003.…”

Section: Discussionmentioning

confidence: 99%

“…growth of the mucosal glands in the ethmoidal segment of the nasal cavity (De las Heras et al, 1993Heras et al, , 2003.…”

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confidence: 99%

Expression of nectin-4 as a potential biomarker in enzootic nasal adenocarcinoma of goats

Aydoğan

Özmen

2016

Acta Veterinaria Hungarica

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The aim of this study was to test nectin-4 by immunohistochemistry as a potential biomarker in enzootic nasal adenocarcinoma (ENA) of goats. Twentyfour archival ENA case samples [from 14 male and 10 female hair goats (Capra hircus)] were used. The samples were stained with haematoxylin and eosin (HE). Nectin-4 expression was studied by immunohistochemistry. By microscopy, tubular, papillary, and mixed patterns of ENA were diagnosed in the cases. Immunohistochemically, the tumours showed moderate nectin-4 expression (++) in 14 cases (58.3%), strong expression (+++) in five cases (20.8%), and weak expression (+) in three cases (12.5%), while two cases (8.3%) were negative. Normal nasal tissues were not stained with nectin-4. The results suggest that nectin-4 may be used as a valuable biomarker of ENA.

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“…JSRV transforms secretory epithelial cells of the distal lung leading to ovine pulmonary adenocarcinoma (OPA) (28,34). ENTV also transforms secretory epithelial cells, although in this case the target cells are located in the nasal mucosa and lead to the formation of a neoplastic disease called enzootic nasal adenocarcinoma (ENA) (9). Two distinct viruses have been implicated in the etiology of ENA, one in sheep (ENTV-1) and one in goats (ENTV-2), and the genomic sequences of both have been determined (7,26,38).…”

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confidence: 99%

Jaagsiekte Sheep Retrovirus and Enzootic Nasal Tumor Virus Promoters Drive Gene Expression in All Airway Epithelial Cells of Mice but Only Induce Tumors in the Alveolar Region of the Lungs

Linnerth-Petrik

Halbert

et al. 2011

J Virol

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Jaagsiekte sheep retrovirus (JSRV) induces tumors in the distal airways of sheep and goats, while the closely related enzootic nasal tumor virus type 1 (ENTV-1) and ENTV-2 induce tumors in the nasal epithelium of sheep and goats, respectively. When expressed using a strong Rous sarcoma virus 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 determining tissue tropism, adeno-associated virus (AAV) vectors expressing alkaline phosphatase under the control of the JSRV, ENTV-1, or ENTV-2 LTRs were generated and administered to mice. The JSRV LTR was active in all airway epithelial cells, while the ENTV LTRs were active in the nasal epithelium and alveolar type II cells but poorly active in tracheal and bronchial epithelial cells. When vectors were administered systemically, the ENTV-1 and -2 LTRs were inactive in major organs examined, whereas the JSRV showed high-level activity in the liver. When a putative transcriptional enhancer from the 3 end of the env gene was inserted upstream of the JSRV and ENTV-1 LTRs in the AAV vectors, a dramatic increase in transgene expression was observed. However, intranasal administration of AAV vectors containing any combination of ENTV or JSRV LTRs and Env proteins induced tumors only in the lower airway. Our results indicate that mice do not provide an adequate model for nasal tumor induction by ENTV despite our ability to express genes in the nasal epithelium.Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) are closely related oncogenic betaretroviruses that infect sheep and goats. These viruses share greater than 90% sequence identity and utilize the same cellular receptor for virus attachment and entry (10, 32), yet they cause distinctly different diseases. JSRV transforms secretory epithelial cells of the distal lung leading to ovine pulmonary adenocarcinoma (OPA) (28,34). ENTV also transforms secretory epithelial cells, although in this case the target cells are located in the nasal mucosa and lead to the formation of a neoplastic disease called enzootic nasal adenocarcinoma (ENA) (9). Two distinct viruses have been implicated in the etiology of ENA, one in sheep (ENTV-1) and one in goats (ENTV-2), and the genomic sequences of both have been determined (7,26,38).It is currently not known how such different diseases result from infection by these closely related retroviruses. Experimental induction of OPA in sheep has been demonstrated using a molecular clone of JSRV (30); however, the lack of a cell culture system capable of propagating ENTV, the fact that an infectious molecular clone of ENTV has not yet been published, and the limitation that experiments using sheep are expensive, have made it difficult to study the mechanism of disease tropism in sheep. Therefore, we developed a model to study JSRV and ENTV tumorigenesis in mice using adenoassociated virus (AAV) vectors (41). AAV vectors made w...

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Enzootic Nasal Adenocarcinoma of Sheep and Goats

Cited by 62 publications

References 25 publications

Characterization of enzootic nasal tumour virus of goats: complete sequence and tissue distribution

Characterization of enzootic nasal tumour virus of goats: complete sequence and tissue distribution

Expression of nectin-4 as a potential biomarker in enzootic nasal adenocarcinoma of goats

Jaagsiekte Sheep Retrovirus and Enzootic Nasal Tumor Virus Promoters Drive Gene Expression in All Airway Epithelial Cells of Mice but Only Induce Tumors in the Alveolar Region of the Lungs

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