Jaagsiekte

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Chris Cousens - One of the best experts on this subject based on the ideXlab platform.

  • Nasal adenocarcinoma associated with Jaagsiekte sheep retrovirus infection in a sheep.
    Journal of Veterinary Diagnostic Investigation, 2019
    Co-Authors: Hanne Jahns, Chris Cousens
    Abstract:

    Betaretrovirus-induced transmissible respiratory tumors in sheep arise at 2 distinct anatomic locations, either deep in the lung tissue caused by Jaagsiekte sheep retrovirus (JSRV) or in the nasal ...

  • Short Communication Prevalence of ovine
    2016
    Co-Authors: Chris Cousens, L. Gibson, J. Finlayson, I. Pritchard, Mark P Dagleish
    Abstract:

    pulmonary adenocarcinoma ( Jaagsiekte) in a UK slaughterhouse sheep stud

  • Jaagsiekte sheep retrovirus infection of lung slice cultures
    Retrovirology, 2015
    Co-Authors: Chris Cousens, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Jeanie Finlayson, Mark P Dagleish, David J. Griffiths
    Abstract:

    BackgroundJaagsiekte 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 in vitro . Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo .ResultsWe describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo . Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA.ConclusionsWe conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

  • Jaagsiekte sheep retrovirus infection of lung slice cultures
    Retrovirology, 2015
    Co-Authors: Chris Cousens, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Jeanie Finlayson, Mark P Dagleish, David J. Griffiths
    Abstract:

    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 in vitro. Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo. We describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo. Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA. We conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

  • Prevalence of ovine pulmonary adenocarcinoma (Jaagsiekte) in a UK slaughterhouse sheep study.
    Veterinary Record, 2015
    Co-Authors: Chris Cousens, Jeanie Finlayson, I. Pritchard, L.l. Gibson, Mark P Dagleish
    Abstract:

    Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA or Jaagsiekte), a disease of increasing concern to sheep farmers. It is an infectious lung cancer caused by viral transformation of type II pneumocytes and Clara cells primarily affecting sheep but goats also (reviewed by Griffiths and others 2010). Generally, older sheep that are clinically affected but lambs less than a year old can show clinical signs. OPA is invariably fatal but the clinical course is highly variable lasting days to weeks. Naive flocks may incur losses of 20–25 per cent to OPA upon initial infection with subsequent annual losses of 1–5 per cent. Affected animals become emaciated, dyspnoeic upon exercise and copious amounts of fluid, which contains large amounts of infectious JSRV (Cousens and others 2009), may drain from the nostrils when the head is lowered. However, many OPA cases fail to produce fluid, and dyspnoeic sheep in poor condition have an extensive differential diagnosis. Preclinical OPA is undetectable by veterinary clinical examination and clinical cases are frequently difficult to diagnose (Cousens and others 2008), yet may still transmit JSRV (Salvatori 2004). Although the causative agent of OPA was determined some time ago (Palmarini and others 1999), no reliable farm-level ante-mortem diagnostic test exists. Antibodies against JSRV are not detectable by serological diagnostic tests (Ortin and others 1998, Scott and others 2013) and PCR-based techniques, although useful research tools, lack sufficient sensitivity in field diagnosis (Lewis and others 2011). Therefore, OPA diagnosis still requires postmortem examination of lungs including histopathology and occasionally immunohistochemistry (IHC). Many dyspnoeic sheep in poor condition are culled without veterinary investigation, so the …

Mark P Dagleish - One of the best experts on this subject based on the ideXlab platform.

  • Short Communication Prevalence of ovine
    2016
    Co-Authors: Chris Cousens, L. Gibson, J. Finlayson, I. Pritchard, Mark P Dagleish
    Abstract:

    pulmonary adenocarcinoma ( Jaagsiekte) in a UK slaughterhouse sheep stud

  • Jaagsiekte sheep retrovirus infection of lung slice cultures
    Retrovirology, 2015
    Co-Authors: Chris Cousens, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Jeanie Finlayson, Mark P Dagleish, David J. Griffiths
    Abstract:

    BackgroundJaagsiekte 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 in vitro . Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo .ResultsWe describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo . Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA.ConclusionsWe conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

  • Jaagsiekte sheep retrovirus infection of lung slice cultures
    Retrovirology, 2015
    Co-Authors: Chris Cousens, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Jeanie Finlayson, Mark P Dagleish, David J. Griffiths
    Abstract:

    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 in vitro. Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo. We describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo. Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA. We conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

  • Prevalence of ovine pulmonary adenocarcinoma (Jaagsiekte) in a UK slaughterhouse sheep study.
    Veterinary Record, 2015
    Co-Authors: Chris Cousens, Jeanie Finlayson, I. Pritchard, L.l. Gibson, Mark P Dagleish
    Abstract:

    Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA or Jaagsiekte), a disease of increasing concern to sheep farmers. It is an infectious lung cancer caused by viral transformation of type II pneumocytes and Clara cells primarily affecting sheep but goats also (reviewed by Griffiths and others 2010). Generally, older sheep that are clinically affected but lambs less than a year old can show clinical signs. OPA is invariably fatal but the clinical course is highly variable lasting days to weeks. Naive flocks may incur losses of 20–25 per cent to OPA upon initial infection with subsequent annual losses of 1–5 per cent. Affected animals become emaciated, dyspnoeic upon exercise and copious amounts of fluid, which contains large amounts of infectious JSRV (Cousens and others 2009), may drain from the nostrils when the head is lowered. However, many OPA cases fail to produce fluid, and dyspnoeic sheep in poor condition have an extensive differential diagnosis. Preclinical OPA is undetectable by veterinary clinical examination and clinical cases are frequently difficult to diagnose (Cousens and others 2008), yet may still transmit JSRV (Salvatori 2004). Although the causative agent of OPA was determined some time ago (Palmarini and others 1999), no reliable farm-level ante-mortem diagnostic test exists. Antibodies against JSRV are not detectable by serological diagnostic tests (Ortin and others 1998, Scott and others 2013) and PCR-based techniques, although useful research tools, lack sufficient sensitivity in field diagnosis (Lewis and others 2011). Therefore, OPA diagnosis still requires postmortem examination of lungs including histopathology and occasionally immunohistochemistry (IHC). Many dyspnoeic sheep in poor condition are culled without veterinary investigation, so the …

  • Short communication: Prevalence of ovine pulmonary adenocarcinoma (Jaagsiekte) in a UK slaughterhouse sheep study
    Veterinary Record, 2015
    Co-Authors: Chris Cousens, Jeanie Finlayson, I. Pritchard, L.l. Gibson, Mark P Dagleish
    Abstract:

    Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA or Jaagsiekte), a disease of increasing concern to sheep farmers. It is an infectious lung cancer caused by viral transformation of type II pneumocytes and Clara cells primarily affecting sheep but goats also (reviewed by Griffiths and others 2010). Generally, older sheep that are clinically affected but lambs less than a year old can show clinical signs. OPA is invariably fatal but the clinical course is highly variable lasting days to weeks. Naive flocks may incur losses of 20–25 per cent to OPA upon initial infection with subsequent annual losses of 1–5 per cent. Affected animals become emaciated, dyspnoeic upon exercise and copious amounts of fluid, which contains large amounts of infectious JSRV (Cousens and others 2009), may drain from the nostrils when the head is lowered. However, many OPA cases fail to produce fluid, and dyspnoeic sheep in poor condition have an extensive differential diagnosis. Preclinical OPA is undetectable by veterinary clinical examination and clinical cases are frequently difficult to diagnose (Cousens and others 2008), yet may still transmit JSRV (Salvatori 2004). Although the causative agent of OPA was determined some time ago (Palmarini and others 1999), no reliable farm-level ante-mortem diagnostic test exists. Antibodies against JSRV are not detectable by serological diagnostic tests (Ortin and others 1998, Scott and others 2013) and PCR-based techniques, although useful research tools, lack sufficient sensitivity in field diagnosis (Lewis and others 2011). Therefore, OPA diagnosis still requires postmortem examination of lungs including histopathology and occasionally immunohistochemistry (IHC). Many dyspnoeic sheep in poor condition are culled without veterinary investigation, so the …

David J. Griffiths - One of the best experts on this subject based on the ideXlab platform.

  • Jaagsiekte sheep retrovirus infection of lung slice cultures
    Retrovirology, 2015
    Co-Authors: Chris Cousens, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Jeanie Finlayson, Mark P Dagleish, David J. Griffiths
    Abstract:

    BackgroundJaagsiekte 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 in vitro . Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo .ResultsWe describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo . Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA.ConclusionsWe conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

  • Jaagsiekte sheep retrovirus infection of lung slice cultures
    Retrovirology, 2015
    Co-Authors: Chris Cousens, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Jeanie Finlayson, Mark P Dagleish, David J. Griffiths
    Abstract:

    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 in vitro. Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo. We describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo. Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA. We conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

  • Diagnosis and control of ovine pulmonary adenocarcinoma (Jaagsiekte)
    In Practice, 2013
    Co-Authors: Phil Scott, David J. Griffiths, Chris Cousens
    Abstract:

    Ovine pulmonary adenocarcinoma (OPA) is a contagious tumour of the lungs of sheep. It is also commonly known as Jaagsiekte, ovine pulmonary carcinoma or sheep pulmonary adenomatosis. OPA is generally considered a chronic wasting disease with progressive respiratory distress leading to emaciation, but it may be that early lung lesions predispose to secondary bacterial pneumonia causing sudden death despite antibiotic treatment. OPA is common in the UK and most other countries where sheep are farmed, but the disease may be grossly under-reported because few deaths are investigated on sheep farms. Disease transmission is facilitated by close confinement such as indoor housing. Effective control, and possible disease eradication, has been hampered by the lack of a suitable diagnostic test or vaccine. This article describes the clinical features of OPA and outlines current methods of diagnosis. Issues surrounding the development of improved diagnostic tests are discussed.

  • Jaagsiekte sheep retrovirus-specific immune responses induced by vaccination: a comparison of immunisation strategies.
    Vaccine, 2006
    Co-Authors: Christina Summers, David J. Griffiths, J. M. Sharp, Patricia Dewar, Christina Cousens, Renate G. Van Der Molen, Daniela Salvatori, Mary Norval
    Abstract:

    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 immunoblotting, and T cell responses by lymphoproliferation assay. Antibodies specific for JSRV-capsid protein were induced by inoculation of recombinant proteins in adjuvant, and transient JSRV-specific T cell responses by intranasal inoculation with inactivated virus. These results will help in the design of a protective vaccine against JSRV infection and the development of OPA.

Massimo Palmarini - One of the best experts on this subject based on the ideXlab platform.

  • Structure of the Capsid Amino-Terminal Domain from the Betaretrovirus, Jaagsiekte Sheep Retrovirus.
    Journal of Molecular Biology, 2008
    Co-Authors: Gulnahar B. Mortuza, David C. Goldstone, Clare Pashley, Lesley F. Haire, Massimo Palmarini, Jonathan Paul Stoye, William R Taylor, Ian A Taylor
    Abstract:

    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 self-association suggests a mode of assembly not driven by the strong capsid carboxy-terminal domain interactions that characterise capsid assembly in the lentiviruses. Based on these data, we propose this structure provides a model for the capsid of betaretroviruses including the HML-2 family of endogenous human betaretroviruses.

  • Jaagsiekte Sheep Retrovirus
    Encyclopedia of Virology, 2008
    Co-Authors: J. M. Sharp, M De Las Heras, Thomas E. Spencer, Massimo Palmarini
    Abstract:

    Jaagsiekte sheep retrovirus (JSRV) and the related small ruminant betaretroviruses are a fascinating group of viruses with unique characteristics that are of broad interest through their veterinary, comparative medical and biological importance. JSRV is the causative agent of ovine pulmonary adenocarcinoma (OPA), an important viral disease of sheep and an outbred animal model for human lung adenocarcinoma. The mechanisms followed by JSRV to transform cells are unique among oncogenic retroviruses as the viral envelope glycoprotein (Env) functions as a dominant oncoprotein. The enzootic nasal tumor virus (ENTV) is also an oncogenic retrovirus highly related both phylogenetically and biologically to JSRV. ENTV induces a contagious tumor of the mucosal nasal glands in sheep and goats. Interestingly, sheep, goats, and most species belonging to the subfamily of the Caprinae, have stably integrated in their genome endogenous retroviruses highly related to ENTV and JSRV (hence the name enJSRVs). enJSRVs are expressed, particularly in the genital tract epithelia of the ewe. Intriguingly, enJSRVs appear critical for sheep placental development during the pre-implantation period and therefore represent a powerful example on how viruses can shape mammalian biology.

  • Molecular Biology of Jaagsiekte Sheep Retrovirus
    Current Topics in Microbiology and Immunology, 2003
    Co-Authors: Massimo Palmarini, Hung Fan
    Abstract:

    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 the past 10 Years, the deduction of the JSRV sequence (York et al. 1991; York 1992), the isolation of an infectious and oncogenic JSRV molecular clone (JSRV21) (Palmarini et al. 1999a) and the establishment of a rapid method to produce infectious virus in vitro (Palmarini et al. 1999a) sparked many studies at the molecular level that strengthened past observations and revealed new properties of this unique virus. Here, we will review the data accumulated so far on the molecular biology of JSRV using the infectious and oncogenic JSRV21 molecular clone as virus of reference.

  • Transformation and Oncogenesis by Jaagsiekte Sheep Retrovirus
    Current Topics in Microbiology and Immunology, 2003
    Co-Authors: Hung Fan, Massimo Palmarini, James C. Demartini
    Abstract:

    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 are described. Molecular cloning of an infectious and oncogenic JSRV provirus was instrumental in the studies. DNA transfection of JSRV proviral DNA into mouse NIH3T3 cells results in morphological transformation, indicating that the JSRV genome carries an oncogene. Further experiments identified the JSRV envelope protein as the transforming gene, and a PI3 kinase docking site in the cytoplasmic tail of the transmembrane (TM) protein was shown to be necessary for transformation. Avian DF-1 cells infected with an avian retroviral vector (RCAS) expressing the JSRV envelope protein also undergo tumorigenic transformation. Possible mechanisms of transformation are discussed, and a cooperating role for insertional activation of proto-oncogenes in tumorigenesis is also considered. The transforming potential of the JSRV envelope protein may be necessary for JSRV infection and replication in vivo.

  • Endogenous retroviruses related to Jaagsiekte sheep retrovirus.
    Current Topics in Microbiology and Immunology, 2003
    Co-Authors: James C. Demartini, Caroline Leroux, Thomas E. Spencer, Jonathan O. Carlson, Massimo Palmarini
    Abstract:

    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 that enJSRV do not directly contribute to the pathogenesis of ovine pulmonary adenocarcinoma (OPA) or enzootic nasal tumor through large-scale recombination events, but small-scale recombination or complementation of gene function cannot be excluded; experiments involving enJSRV-free sheep, which have not been found, would be needed to investigate this possibility. Evidence of expression of enJSRV structural proteins in tissues of the reproductive tract and lung implies that they do not have a primary role in disease. However, experimental exploitation of exogenous/endogenous retrovirus sequence differences by producing chimeras has been useful in establishing the determinants of JSRV Envinduced transformation. Even if enJSRV do not have a direct role in OPA, their expression during ontogeny or in neonatal life may impact the likelihood of exogenous JSRV infection and disease outcome via the induction of immunological tolerance. Aside from any role in disease, enJSRV loci may serve as useful genetic markers in the sheep and their frequent expression in the reproductive tract of the ewe may portend an important physiologic role in sheep.

Jeanie Finlayson - One of the best experts on this subject based on the ideXlab platform.

  • Jaagsiekte sheep retrovirus infection of lung slice cultures
    Retrovirology, 2015
    Co-Authors: Chris Cousens, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Jeanie Finlayson, Mark P Dagleish, David J. Griffiths
    Abstract:

    BackgroundJaagsiekte 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 in vitro . Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo .ResultsWe describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo . Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA.ConclusionsWe conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

  • Jaagsiekte sheep retrovirus infection of lung slice cultures
    Retrovirology, 2015
    Co-Authors: Chris Cousens, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Jeanie Finlayson, Mark P Dagleish, David J. Griffiths
    Abstract:

    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 in vitro. Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo. We describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo. Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA. We conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

  • Prevalence of ovine pulmonary adenocarcinoma (Jaagsiekte) in a UK slaughterhouse sheep study.
    Veterinary Record, 2015
    Co-Authors: Chris Cousens, Jeanie Finlayson, I. Pritchard, L.l. Gibson, Mark P Dagleish
    Abstract:

    Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA or Jaagsiekte), a disease of increasing concern to sheep farmers. It is an infectious lung cancer caused by viral transformation of type II pneumocytes and Clara cells primarily affecting sheep but goats also (reviewed by Griffiths and others 2010). Generally, older sheep that are clinically affected but lambs less than a year old can show clinical signs. OPA is invariably fatal but the clinical course is highly variable lasting days to weeks. Naive flocks may incur losses of 20–25 per cent to OPA upon initial infection with subsequent annual losses of 1–5 per cent. Affected animals become emaciated, dyspnoeic upon exercise and copious amounts of fluid, which contains large amounts of infectious JSRV (Cousens and others 2009), may drain from the nostrils when the head is lowered. However, many OPA cases fail to produce fluid, and dyspnoeic sheep in poor condition have an extensive differential diagnosis. Preclinical OPA is undetectable by veterinary clinical examination and clinical cases are frequently difficult to diagnose (Cousens and others 2008), yet may still transmit JSRV (Salvatori 2004). Although the causative agent of OPA was determined some time ago (Palmarini and others 1999), no reliable farm-level ante-mortem diagnostic test exists. Antibodies against JSRV are not detectable by serological diagnostic tests (Ortin and others 1998, Scott and others 2013) and PCR-based techniques, although useful research tools, lack sufficient sensitivity in field diagnosis (Lewis and others 2011). Therefore, OPA diagnosis still requires postmortem examination of lungs including histopathology and occasionally immunohistochemistry (IHC). Many dyspnoeic sheep in poor condition are culled without veterinary investigation, so the …

  • Short communication: Prevalence of ovine pulmonary adenocarcinoma (Jaagsiekte) in a UK slaughterhouse sheep study
    Veterinary Record, 2015
    Co-Authors: Chris Cousens, Jeanie Finlayson, I. Pritchard, L.l. Gibson, Mark P Dagleish
    Abstract:

    Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA or Jaagsiekte), a disease of increasing concern to sheep farmers. It is an infectious lung cancer caused by viral transformation of type II pneumocytes and Clara cells primarily affecting sheep but goats also (reviewed by Griffiths and others 2010). Generally, older sheep that are clinically affected but lambs less than a year old can show clinical signs. OPA is invariably fatal but the clinical course is highly variable lasting days to weeks. Naive flocks may incur losses of 20–25 per cent to OPA upon initial infection with subsequent annual losses of 1–5 per cent. Affected animals become emaciated, dyspnoeic upon exercise and copious amounts of fluid, which contains large amounts of infectious JSRV (Cousens and others 2009), may drain from the nostrils when the head is lowered. However, many OPA cases fail to produce fluid, and dyspnoeic sheep in poor condition have an extensive differential diagnosis. Preclinical OPA is undetectable by veterinary clinical examination and clinical cases are frequently difficult to diagnose (Cousens and others 2008), yet may still transmit JSRV (Salvatori 2004). Although the causative agent of OPA was determined some time ago (Palmarini and others 1999), no reliable farm-level ante-mortem diagnostic test exists. Antibodies against JSRV are not detectable by serological diagnostic tests (Ortin and others 1998, Scott and others 2013) and PCR-based techniques, although useful research tools, lack sufficient sensitivity in field diagnosis (Lewis and others 2011). Therefore, OPA diagnosis still requires postmortem examination of lungs including histopathology and occasionally immunohistochemistry (IHC). Many dyspnoeic sheep in poor condition are culled without veterinary investigation, so the …

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