Multiple copies of Shope virus DNA are present in cells of benign and malignant non-virus-producing neoplasms

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Cottontail rabbit papillomavirus induces strictly epithelial tumors in both cottontail and domestic rabbits. A high proportion of the initial benign papillomas progress within 8 to 14 months to invasive carcinomas. With the help of mRNA-specific riboprobes for E6, E7, El, E2, LI, and L2, we investigated by in situ hybridization the RNA expression pattern of cottontail rabbit papillomavirus in tissue sections of biopsies from different stages of tumor development. Common features of all lesions were high levels of E6 and E7 mRNAs and low levels of El and E2 mRNAs. In agreement with earlier reports, there was no evidence for a major mRNA class equivalent to the prominent El^E4 RNA of human papillomavirus types 6/11 and 16. In cottontail rabbit papillomas, high levels of E6 and E7 mRNAs were present in the upper differentiated epithelial layers. These layers also contained most of the El and E2 mRNAs and the viral DNA. In contrast, papillomas of domestic rabbits revealed the opposite differentiation-dependent expression pattern for the E6 and E7 mRNAs; there were strong signals in the basal layers, and these declined with increased differentiation. Transcripts encoding the LI mRNA were detected only in a few isolated cells of the granular layer. There was no difference between the amounts of E6, E7, El, and E2 mRNAs present in highly dysplastic tissue and those present in adjacent normal papillomatous epithelium within a progressing papilloma. However, late transcripts and viral DNA detectable only in the upper layers of the papilloma were present throughout the thickness of the dysplastic tissue, indicating a newly acquired permissiveness of the dysplastic cells for viral DNA replication and late transcription. Carcinomas in general had the same expression patterns for E6, E7, and El but were dissimilar in the levels of expression of E2 and late transcripts.

Section: Discussionmentioning

confidence: 99%

Changes in RNA expression pattern during the malignant progression of cottontail rabbit papillomavirus-induced tumors in rabbits

Zeltner

Borenstein

Wettstein

et al. 1994

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“…Animals, viruses, and VX-7 cell lines. The sources of animals and virus and the mode of infection were described previously (14). The cell line derived from the transplantable VX-7 tumor (7a) was grown in Eagle minimal essential medium plus nonessential amino acids and 10o bovine serum at 37°C in 5% CO2.…”

Section: Methodsmentioning

confidence: 99%

Two colinear and spliced viral transcripts are present in non-virus-producing benign and malignant neoplasms induced by the shope (rabbit) papilloma virus

Nasseri¹,

Wettstein²,

Stevens³

1982

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The nature of Shope virus-specific RNA was investigated in non-virus-producing Shope (rabbit) papilloma virus-induced benign and malignant domestic rabbit tumors and in a cell line derived from the VX-7 transplantable carcinoma. RNA transfer (Northern) blot analysis of polyadenylated RNA isolated from whole cell extracts of all three sources was resolved into two major bands of 1.3 and 2.0 kilobases. Two additional minor bands of 3.5 and 4.8 kilobases could be seen in some analyses. RNA of the VX-7 cell line was further separated into nuclear, cytoplasmic, and polysomal fractions. The cytoplasmic fraction only contained the 1.3-and 2.0-kilobase species, and virus-specific RNA was found to be associated with polysomes. The two major transcripts present in VX-7 cells were mapped by hybridization of RNA transfer blots with subgenomic probes, and the results indicated that both transcripts are spliced and are most likely colinear. Our results are consistent with the suggestion that the two viral transcripts are necessary for induction and maintenance of the neoplasms.

“…Animals, virus, and sera. Cottontail rabbits obtained from E. Johnson, Rego, Kans., were infected with the Washington B strain of CRPV by intradermal injection (29), and sera were taken 4 to 6 months after infection at the papilloma stage, as previously described (20). New Zealand White (NZW) rabbits obtained from Irish Farms (Norco, Calif.)…”

Section: Materuils and Methodsmentioning

confidence: 99%

Cottontail rabbit papillomavirus L1 protein-based vaccines: protection is achieved only with a full-length, nondenatured product

Lin

Borenstein

Ahmed

et al. 1993

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