WordNet

woolly usually horned ruminant mammal related to the goat
a docile and vulnerable person who would rather follow than make an independent decision; "his students followed him like sheep"
a timid defenseless simpleton who is readily preyed upon
any of a group of viruses that contain two single-strand linear RNA molecules per virion and reverse transcriptase (RNA to DNA); the virus transcribes its RNA into a cDNA provirus that is then incorporated into the host cell

PrepTutorEJDIC

羊 / 気の弱い人,人に引きずられやすい人
『彼女は』,『彼女が』 / 《月・船・汽車・都市・国などを指して》それは,それが / 女,婦人;(動物の)雌

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/03/01 21:03:07」(JST)

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Jaagsiekte sheep retrovirus (JSRV) is a betaretrovirus which is the causative agent of a contagious lung cancer in sheep called Jaagsiekte, or Ovine Pulmonary Adenocarcinoma (OPA).

Natural history[edit]

JSRV is the virus that is the etiologic agent responsible for contagious lung tumors in sheep called Ovine Pulmonary Adenocarcinoma (OPA) .The disease was called “Jaagsiekte”, after the Afrikaans words for “chase” (Jaag) and “sickness” (siekte), to describe the respiratory distress observed in an animal out of breath from being chased indicating the breathing difficulty that infected sheep have . Transmission of virus is through aerosol spread between sheep.

Exogenous infectious form of JSRV has an endogenous counterpart which is present in the genomes of all sheep and goats.^[1] The sheep genome has around 27 copies of endogenous retroviruses (enJSRVs) that are closely related to JSRV. Endogenous JSRV has several roles in the evolution of the domestic sheep as they are able to block the JSRV replication cycle and play a critical role in sheep conceptus development and placental morphogenesis.^[2]

Although OPA resembles human lung cancer, human lung cancer is not known to be caused by betaretroviruses.^[3] Even though a possibility of viral etiology has been eliminated in bronchoalveolar cancer, understanding the molecular mechanisms leading to the transformation of lung epithelia by JSRV may be of interest in the context of therapeutic approaches in human lung cancers in general and bronchoalveolar adenocarcinoma (BAC) in particular.^[4]

Classification[edit]

JSRV belongs to the family Retroviridae, to the subfamily Orthoretrovirinae and the genus Betaretrovirus.

Pathogenesis[edit]

JSRV is transmitted by the respiratory route and may also infect lymphocytes and myeloid cells, in addition to the lung epithelia. Expression of the JSRV Envelope protein activates signalling cascades that promote cellular proliferation and malignant transformation of the cells. Initially, the tumour cells grow along the alveolar walls in a pattern reminiscent of human BAC, but subsequently become more invasive and metastasize to the local lymphnodes. Larger tumours maybe necrotic and fibromatous at their centre.As the tumour grows, fluid production in the lung increases and this is likely to promote virus spread to other sheep. Only when the tumour reaches a size large enough to compromise lung function, do clinical signs appear. Critically,the majority of infected animals in endemic areas never show outward signs of infection, but they may be shedding virus, thus promoting inadvertent introduction of the disease into previously unaffected flocks and new geographical areas.^[5]

Genome structure[edit]

The genome of the exogenous virus is 7462 bases and has the classical "gag", "pol", "env" genome arrangement and is flanked by a long terminal repeat (LTR) on each end. There are 4 genes that encode the viral structural proteins. They are "gag" encoding the structural internal virion proteins comprising "matrix" (MA), "capsid" (CA) and "nucleocapsid"(NC); "pro", which encodes an aspartic protease (PR); "pol", which encodes the" RT" and "integrase"(IN) enzymes; and "env", which encodes the "surface" (SU) and "transmembrane "(TM) envelope glycoproteins. The viral proteins are synthesized initially as large precursors and are later processed into the mature proteins by proteolytic cleavage.^[6] An additional open reading frame(ORF) was observed in the viral genome and has been called orfX and its function is undefined.^[7]

Replication cycle[edit]

The initial attachment of JSRV to its target cell is mediated through the binding of the SU subunit of the Env glycoprotein to a specific cell surface receptor molecule,"Hyal2". The entry of the JSRV core into the cytoplasm activates reverse transcription, during which the single-stranded RNA genome is converted into a double-stranded DNA form and gets integrated as a provirus into the host. Following integration, expression of JSRV RNA from the viral promoter in the LTR is controlled by the host transcriptional machine. Following transcription and translation of the viral genome, the new progeny virus gets assembled at the plasma membrane and bud off from the host cell acquiring a lipid envelope and their "env" glycoproteins. Following release from the cell, the "Gag"-"Pro"-"Pol" polyproteins are cleaved into their mature forms by Protease. This step maturation is essential for the formation of infectious particles.^[8]

Receptor and Entry[edit]

The cellular receptor for JSRV is hyaluronidase 2 (Hyal2), a glycophosphatidylinol(GPI)-anchored protein belonging to the hyaluronidase family. Generally, oncogenic retroviruses cause transformation of host cells mostly by insertional activation of a host proto oncogene into an oncogene. But JSRV is different in this aspect since its envelope glycoprotein ("env") by itself is an oncogene and this single protein was shown to be necessary and sufficient to induce lung tumors in sheep.^[9] Unlike the majority of retroviruses, JSRV entry into the host cell is pH-dependent. Thus oncogenic JSRV has borrowed features of both pH-dependent and pH-independent viruses for entry which involves both the receptor binding and a low pH for fusion transformation of host cells.^[10]

Host immune response[edit]

An important feature of JSRV infection is the absence of any specific immune response from the host. A likely explanation is that the sheep are immunologically tolerant to JSRV antigens due to the expression of closely related endogenous JSRV proteins in the fetal thymus during T lymphocyte development and any JSRV-reactive T cells should be recognized as ‘anti-self’ and selectively removed. Another hypothesis is that tumor cells downregulate their major histocompatibility class-I expression, possibly being the reason for the absence of any virus-specific cytotoxic T cell response (CTL).^[5]

References[edit]

^ York DF et al (2003) A history of ovine pulmonary adenocarcinoma (jaagsiekte) and experiments leading to the deduction of the JSRV nucleotide sequence. Curr Top Microbiol Immunol 275:1–23. [PMID 12596893]
^ Arnaud F et al (2008) Coevolution of endogenous betaretroviruses of sheep and their host. CMLS 65(21):3422–3432 [PMID 18818869]
^ Hopwood et al (2010) Hum Pathol. Absence of markers of betaretrovirus infection in human pulmonary adenocarcinoma. 41(11):1631–40 [PMID 20825971]
^ Leroux C et al (2007) Jaagsiekte Sheep Retrovirus (JSRV):from virus to lung cancer in sheep. Vet Res 38 211–228 [PMID 17257570]
^ ^a ^b Griffiths et al, J. Comp. Path. 2010, Vol. 142, 260e283 "Pathology and Pathogenesis of Ovine Pulmonary Adenocarcinoma" [PMID 20163805]
^ Griffiths et al,"Pathology and Pathogenesis of Ovine Pulmonary Adenocarcinoma" J. Comp. Path. 2010, Vol. 142, 260e283 [PMID 20163805]
^ YorkJF et al. "A history of ovine pulmonary adenocarcinoma (jaagsiekte) and experiments leading to the deduction of the JSRV nucleotide sequence." Curr Top Microbiol Immunol. 2003;275:1–23. [PMID 12596893]
^ Griffiths et al, J. Comp. Path. 2010, Vol. 142, 260e283 "Pathology and Pathogenesis of Ovine pulmonary Adenocarcinoma" [PMID 20163805]
^ Palmarini et al "Expression of the jaagsiekte sheep retrovirus envelope glycoprotein is sufficient to induce lung tumors in sheep".) J Virol. 2006 Aug;80(16):8030–7 [PMID 16873259]
^ Cote et al. J Virol. 2009 Nov;83(22):11447–55."Receptor binding and low pH coactivate oncogenic retrovirus envelope-mediated fusion" [PMID 19726505]

Palmarini M, Fan H (2003). "Molecular biology of Jaagsiekte sheep retrovirus". Curr. Top. Microbiol. Immunol. 275: 81–115. PMID 12596896.
Sharp JM, DeMartini JC (2003). "Natural history of JSRV in sheep". Curr. Top. Microbiol. Immunol. 275: 55–79. PMID 12596895.

UpToDate Contents

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1. 細気管支肺胞上皮癌（上皮内腺癌） bronchioloalveolar carcinoma including adenocarcinoma in situ

English Journal

Expression of endogenous beta retroviruses and Hyal-2 mRNA in immune organs of fetuses and lambs.

Qi JW, Wu XL, Liu SY, Cao GF.SourceCollege of Animal Science and Veterinary Medicine, Inner Mongolia Agricultural University, Huhhot, 010018, China.
Virologica Sinica.Virol Sin.2012 Apr;27(2):83-92. Epub 2012 Apr 11.
Endogenous beta retroviruses (enJSRV) are highly homologous with Jaagsiekte sheep retrovirus (exJSRV), this exogenous retrovirus is the aetiological agent of ovine pulmonary adenocarcinoma (OPA). The aim of this study was to clarify the function of enJSRV and the immunological mechanisms of its corr
PMID 22491999

The distribution of immune cells in the lungs of classical and atypical ovine pulmonary adenocarcinoma.

Summers C, Benito A, Ortin A, Garcia de Jalon JA, González L, Norval M, Sharp JM, De las Heras M.SourceDepartmento de Patologia Animal, Facultad de Veterinaria, Universidad de Zaragoza, c/Miguel Servet 177, 50013 Zaragoza, Spain.
Veterinary immunology and immunopathology.Vet Immunol Immunopathol.2012 Mar 15;146(1):1-7. Epub 2012 Jan 18.
Ovine pulmonary adenocarcinoma (OPA) is a contagious tumour caused by infection of sheep with Jaagsiekte sheep retrovirus. Two forms of OPA have been identified, classical and atypical, which can be distinguished clinically and pathologically. Most notably classical OPA is progressive until death, w
PMID 22341799

Japanese Journal

Endogenous Retroviruses of Sheep : A Model System for Understanding Physiological Adaptation to an Evolving Ruminant Genome

,
The Journal of reproduction and development 58(1), 33-37, 2012-02-01
… Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. … The sheep genome contains 27 endogenous betaretroviruses (enJSRVs) related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. …
NAID 10030406909

Surveillance of Jaagsiekte Sheep Retrovirus in Sheep in Hokkaido, the Northern Island of Japan

, , [他],
Journal of Veterinary Medical Science 73(11), 1493-1495, 2011
… Surveillance of jaagsiekte sheep retrovirus (JSRV) infection was performed by polymerase chain reaction (PCR) of blood DNA samples collected from 40 sheep and goats in 10 different flocks in Hokkaido, the northern island of Japan. … No exogenous (oncogenic) JSRV sequence was detected by PCR in these samples, while the ovine endogenous retrovirus sequence was successfully amplified in all samples. …
NAID 130000861825

動物由来レトロウイルスの受容体

宮沢孝幸
ウイルス 59(2), 223-242, 2009
　レトロウイルス感染症は獣医学領域において古くから問題となっている．家畜や伴侶動物は様々なレトロウイルスに感染している．ウイルスの受容体（レセプター）を明らかにすることは，病理発生機構の解明，感染や発症を阻止する薬の開発，外来遺伝子導入用レトロウイルスベクターの開発などに役に立つ．獣医学領域で問題になっているレトロウイルスのうち，現在までにウマ伝染性貧血症ウイルス，ネコ免疫不全ウイルス，ネコ白血病 …
NAID 130004470932

Related Pictures

★リンクテーブル★

リンク元	「JSRV」「ヤーグジークテヒツジレトロウイルス」
関連記事	「sheep」「jaagsiekte」「retrovirus」

「JSRV」

Jaagsiekte Sheep Retrovirus
Virus classification
Group:	Group VI (ssRNA-RT)
Family:	Retroviridae
Subfamily:	Orthoretrovirinae
Genus:	Betaretrovirus
Species:	Jaagsiekte sheep retrovirus