Expression of the Jaagsiekte Sheep Retrovirus Envelope Glycoprotein Is Sufficient To Induce Lung Tumors in Sheep
作者： Marco Caporale , Christina Cousens , Patrizia Centorame , Chiara Pinoni , Marcelo De las Heras
DOI: 10.1128/JVI.00474-06
关键词:
摘要: Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA). The expression JSRV envelope (Env) alone sufficient to transform a variety cell lines in vitro and induce lung cancer immunodeficient mice. In order determine role Env OPA tumorigenesis sheep, we derived replication-defective virus (JS-RD) which expresses env under control its own long terminal repeat (LTR). JS-RD was produced by transiently transfecting 293T cells with two plasmid system, involving (i) packaging plasmid, putative signal deleted, expressing structural enzymatic proteins Gag, Pro, Pol, (ii) trans for particles provides genomes necessary deliver upon infection. During optimization system determined that both R-U5 (in viral 5' LTR) region are important particle production. Two independent experimental transmission studies were carried out newborn lambs. Four five lambs inoculated showed lesions lungs at various times between 4 12 months postinoculation. Abundant detected tumor JS-RD-infected animals PCR assays confirmed presence deleted genome. These data strongly suggest functions as dominant oncoprotein natural immunocompetent host can absence spread.
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