Jaagsiekte sheep retrovirus
Jaagsiekte sheep retrovirus | |
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Virus classification | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Pararnavirae |
Phylum: | Artverviricota |
Class: | Revtraviricetes |
Order: | Ortervirales |
Family: | Retroviridae |
Genus: | Betaretrovirus |
Species: | Jaagsiekte sheep retrovirus
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Jaagsiekte sheep retrovirus (JSRV) is a betaretrovirus which is the causative agent of a contagious lung cancer in sheep, called ovine pulmonary adenocarcinoma.
Natural history
JSRV is the virus that is the cause of the contagious lung tumors in sheep called ovine pulmonary adenocarcinoma (OPA). The disease has also been 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 experienced by infected sheep. Transmission of virus is through aerosol spread between sheep.[citation needed]
The
Although OPA resembles human lung cancer, human lung cancer is not known to be caused by betaretroviruses.[3] Even though a possibility of a viral cause 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
JSRV belongs to the family ]
Pathogenesis
JSRV is transmitted by the respiratory route and may also infect
Genome structure
The genome of the exogenous virus is 7462 bases and has the classical "gag", "pol", "env" genome arrangement and is flanked by a
Replication cycle
The initial attachment of JSRV to its target cell is mediated through the binding of the SU subunit of the Env
Receptor and entry
The cellular
Host immune response
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
Endogenous jaagsiekte sheep retrovirus
During evolution, the sheep genome incorporated parts of the Jaagksiete sheep retrovirus, now known as endogenous Jaagsiekte sheep retrovirus (enJSRV).[8] There are 27 known copies of enJSRV in the sheep genome, of which five show intact sequences found in all retroviruses.[2][9] These seem to have been adopted by the sheep genome as enJSRV aids placental development and provides protection against similar retroviruses.[8][9] In vitro assays have found that enJSRV does this by blocking various stages of the viral replication cycle.[2][9][10] An example of this protection is seen in ovine endometrial epithelium where the high expression of enJSVR prevents exogenous JSVR from entering the cells via blocking the common receptor to both, HYAL2.[9] However, Jaagsiekte virus can sometimes mutate to overcome this protection, and there is evidence of this having occurred in the last 200 years.[8] There is also indication that the endogenization of Jaagsiekte virus is still occurring today.[2]
enJSRV mechanism in reproduction
In sheep, enJSRVs are highly expressed in the
HYAL2
Hyaluronidase 2 (HYAL2) serves as a cell-surface receptor for both the exogenous and endogenous JSRV envelope (env). HYAL2 mRNA can be detected in the BNCs and multinucleated syncytia of sheep placentomes during pregnancy, but not in the trophectoderm cells or any cells of the endometrium.[12] In situ hybridization analysis revealed that HYAL2 mRNA was only detected in the binucleate cells and multi-nucleated syncytial plaques.[10] It is hypothesised that enJSRV interactions with HYAL2 are vital for placental growth and differentiation.[11] Whilst the cellular and molecular mechanism are still unclear, it is apparent it has a role in protecting the uterus against viral infection and placental morphogenesis.[10]
The co-expression of the enJSRV envelope and HYAL2 in the same cell types supports the hypothesis that HYAL2 binds to enJSRVs env on the binucleate cells and promotes their fusion into multi-nucleated syncytia.[8]
Comparative physiology in humans and mice
Of interest for comparative physiology is that the presence of enJSRV envelope protein expression in the developing sheep placenta is very similar to that observed for syncytin in humans and the mouse.[14] During the formation of the human placenta syncytiotrophoblast, by fusion of mononuclear cytotrophoblasts, human syncytins are specifically expressed. The syncytins are fusogenic when expressed in vitro, supporting the hypothesis that they are involved in placental morphogenesis.[8] These observations support the theory that an ancient retroviral infection had important consequences for mammalian evolution.[8] The involvement of the betaretrovirus enJSRV in the sheep conceptus trophoblasts further argues for its involvement in sheep placentation.[8]
Future directions and summary
Research surrounding endogenous retroviruses supports the idea that they may play critical roles in conceptus growth, placental differentiation and cell fusion in mammals. The morphological aspects of binucleate cell differentiation in ruminants such as sheep are well characterised, but the mechanisms are not well defined - though evidence shows that enJSRV RNA and HYAL2 mRNA are co-expressed in the binucleate cell and multinucleated syncytiotrophoblasts throughout gestation.[citation needed]
See also
References
Further reading
- Palmarini M, Fan H (2003). "Molecular Biology of Jaagsiekte Sheep Retrovirus". Jaagsiekte Sheep Retrovirus and Lung Cancer. Current Topics in Microbiology and Immunology. Vol. 275. pp. 81–115. PMID 12596896.
- Sharp JM, DeMartini JC (2003). "Natural History of JSRV in Sheep". Jaagsiekte Sheep Retrovirus and Lung Cancer. Current Topics in Microbiology and Immunology. Vol. 275. pp. 55–79. PMID 12596895.