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. 2007 Oct 25;367(2):413-21.
doi: 10.1016/j.virol.2007.06.004. Epub 2007 Jul 3.

In vivo tumorigenesis by Jaagsiekte sheep retrovirus (JSRV) requires Y590 in Env TM, but not full-length orfX open reading frame

Chris Cousens  1 , Naoyoshi Maeda, Claudio Murgia, Mark P Dagleish, Massimo Palmarini, Hung Fan
Affiliations

In vivo tumorigenesis by Jaagsiekte sheep retrovirus (JSRV) requires Y590 in Env TM, but not full-length orfX open reading frame

Chris Cousens et al. Virology. .

Abstract

Jaagsiekte retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep. The envelope (Env) glycoprotein protein of JSRV functions as a dominant oncoprotein in vitro and in vivo. An SH2 binding domain (YXXM) in the cytoplasmic tail of the JSRV Env is one of the main determinants of viral transformation at least in vitro. In these studies, we report the first in vivo tests of site-specific mutants of JSRV in their natural host, the sheep. We show that, in vivo, JSRV(21) with the cytoplasmic tail YXXM mutated to DXXM did not cause disease nor detectable infection, indicating that this motif is absolutely required for virus replication and possibly transformation in vivo. In contrast, mutation of the JSRV open reading frame orfX, for which no function has yet been attributed, did not alter the disease induced by JSRV(21).

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Figures

Figure 1
Figure 1. Replication capacity of JSRVΔorfX
Sheep choroid plexus cells (CP-1) were infected with i) heat-inactivated JSRV21, ii) JSRV21, iii) heat-inactivated ΔorfXJSRV or iv) ΔorfXJSRV, and serially passaged. At different passages DNA was extracted from the cells and tested by PCR for the presence of proviral JSRV DNA. Representative PCR results from an intermediate passage are shown (ca. passage 6); PCR signals for both wild-type and ΔorfX JSRV were detectable at equivalent levels through passage 23. No PCR signals were detected in the cultures infected with heat-inactivated viruses. +: PCR positive control, pCMV2JS21 plasmid DNA. -: PCR negative control, water.
Figure 2
Figure 2. Comparison of JSRV dose in the inocula
a. Western blot comparison of JSRV. 5μl of inoculum run on a 10% SDS-PAGE gel, electro blotted onto nitrocellulose and reacted with 1:200 antiserum JS382 (raised against recombinant JSRV CA protein (Salvatori et al., 2004)). b. qRT-PCR estimation of JSRV copy number. Serially diluted in vitro transcribed RNA was used as standard from which to estimate the RNA copy number of the JSRV in 5ml of inoculum. Error bars shown are the standard error of the mean from four replicates.
Figure 3
Figure 3. Histology of experimentally-induced OPA
Haematoxylin & eosin stained sections of OPA induced by a) JSRV21 and b) JSRVΔorfX show indistinguishable tumours composed of papillary proliferation of cuboidal epithelial cells in the lung parenchyma irrespective of whether they were induced by the wild-type or Δorfx virus.
See this image and copyright information in PMC

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