Abstract
Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a lung cancer in sheep known as ovine pulmonary adenocarcinoma (OPA). The disease has been identified around the world in several breeds of sheep and goats, and JSRV infection typically has a serious impact on affected flocks. In addition, studies on OPA are an excellent model for human lung carcinogenesis. A unique feature of JSRV is that its envelope (Env) protein functions as an oncogene. The JSRV Env-induced transformation or oncogenesis has been studied in a variety of cell systems and in animal models. Moreover, JSRV studies have provided insights into retroviral genomic RNA export/expression mechanisms. JSRV encodes a trans-acting factor (Rej) within the env gene necessary for the synthesis of Gag protein from unspliced viral RNA. This review summarizes research pertaining to JSRV-induced pathogenesis, Env transformation, and other aspects of JSRV biology.
Highlights
Ovine pulmonary adenocarcinoma (OPA) is a contagious neoplasm affecting sheep lungs [1,2,3].The disease has been described in various breeds of sheep and rarely in goats, but it does not affect cattle or other animals [4]
We have found a composite cis-acting RNA element in the 3’ end of the jaagsiekte sheep retrovirus (JSRV) env gene that contains 1) a constitutive transport element (CTE) that facilitates export of full-length viral RNAs in most cells, and 2) a Rej-binding element (RejRE) that facilitates export of unspliced viral RNA in 293T cells and that is required for translation of unspliced viral mRNA in all cells [131]
JSRV is unique among retroviruses in that it is an acute transforming virus whose oncogene is its Envelope structural protein
Summary
Ovine pulmonary adenocarcinoma (OPA) is a contagious neoplasm affecting sheep lungs [1,2,3]. In the U.K. and South Africa, OPA accounts for almost 70% of all sheep tumors [4]. A field test for OPA, known as the wheelbarrow assay, is performed by elevating the body cavity of the sheep over the mouth, at which point lung fluid drains from the nose of infected sheep (Figure 4A). While this assay has been important for diagnosing OPA, the lung fluid from infected sheep has been invaluable experimentally. While practical efforts have focused on controlling the disease, our current understanding of OPA has benefited from dissecting the molecular and biochemical aspects of the causative agent, jaagsiekte sheep retrovirus (JSRV).
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