Oncogenicity of avian leukosis viruses of different subgroups and of mutants of sarcoma viruses

When injected into chickens, a transformation-defective mutant of the Prague C strain of Rous sarcoma virus induced tumors at low incidence and after a long latency. One such tumor released a replication-defective virus designated PR2257. We molecularly cloned and sequenced the proviral DNA from quail fibroblasts transformed by PR2257. Comparison of PR2257 sequence with that of Prague C, cellular src, and 3' adjacent cellular DNA showed that the spliced version of the c-src gene and about 950 base pairs (bp) of 3'-flanking cellular DNA were transduced into PR2257. This transduction eliminated nearly all replicative genes, since the gag gene splice donor site was linked to the splice acceptor site of the src gene and, on the 3' side, recombination occurred in the end of env gene. Insertion of two extra cytosines 23 bp before and 19 bp after the c-src stop codon resulted in an extension of the coding portion up to 587 amino acids, divergence of sequences after Pro-525 and replacement of Tyr-527 by a valine residue. In addition, it appears that the 5' and 3' untranslated regions of PR2257 result from multiple recombinations between exogenous and endogenous virus genomes. Limited digestion of p66src encoded by PR2257 with Staphylococcus aureus V8 protease yielded a V2 peptide (C-terminal moiety) with an apparent molecular mass of 31 kilodaltons, consistent with the 5.7-kilodalton increase expected from the DNA sequence. The structure of PR2257 suggests that the first step in the capture of c-src gene by avian lymphomatosis viruses is the trans splicing of the viral leader mRNA to exon 1 of c-src.

mentioning

confidence: 99%

Transduction of the cellular src gene and 3' adjacent sequences in avian sarcoma virus PR2257

Geryk

Dezélée

Barnier

et al. 1989

“…The avian leukosis viruses (ALVs), which do not carry oncogenes, usually induce neoplasia after a latent period of 4 to 12 months, and the incidence of neoplasia is generally lower (20 to 80%) than that of the acute viruses. The most common neoplasm in ALV-infected chickens is lymphoid leukosis (a B-cell lymphoma originating in the bursa of Fabricius), but other diseases such as nephroblastoma, fibrosarcoma, osteopetrosis, and erythroblastosis also occur (3,50). The spectrum and incidence of these neoplasms are influenced by a number of factors, including virus strain, virus titer, site of inoculation, and the age and genetic makeup of the host (2, 9, 50).…”

mentioning

confidence: 99%

Genetic determinants of neoplastic diseases induced by a subgroup F avian leukosis virus

Simon¹,

Neckameyer²,

Hayward³

et al. 1987

Two subgroup F avian leukosis viruses, ring-necked pheasant virus (RPV) and RAV-61, were previously shown to induce a high incidence of a fatal proliferative disorder in the lungs of infected chickens. These lung lesions, termed angiosarcomas, appear rapidly (4 to 5 weeks after infection), show no evidence of protooncogene activation by proviral integration, and are not induced by avian leukosis viruses belonging to other subgroups. To identify the viral sequences responsible for induction of these tumors, we constructed recombinant viruses by exchanging genomic segments of molecularly cloned RPV with those of a subgroup A leukosis virus, UR2AV. The ability to induce rapid lung tumors segregated only with the env sequences of RPV; the long terminal repeat of RPV was not required. However, recombinants carrying both env and long terminal repeat sequences of RPV induced lung tumors with a shorter latency. In several cases, recombinant viruses exhibited pathogenic properties differing from those of either parental virus. Recombinants carrying the gag-pol region of RPV and the env gene of UR2AV induced a high incidence of a muscle lesion termed infiltrative intramuscular fibromatosis. One recombinant, EU-8, which carries the gag-pol and LTR sequences of RPV, and the env gene of UR2AV, induced lymphoid leukosis after an unusually short latent period. The median time of death from lymphoid leukosis was 6 to 7 weeks after infection with EU-8 compared with approximately S months for UR2AV.

“…MAV-1(0) (subgroup A) and MAV-2(0) (subgroup B) induce a preponderance of osteopetrosis (30), MAV-2(N) (subgroup B) induces primarily nephroblastoma (37), and RPV (subgroup F) induces rapid appearance of lung angiosarcomas (6). The remaining viruses examined induce a variety of diseases, predominately lymphoid leukosis, usually after a long latent period (24).…”

mentioning

confidence: 99%

Specificity of avian leukosis virus-induced hyperlipidemia

Carter¹,

Smith²

1984

Rous-associated virus 7 (RAV-7) is a subgroup C avian leukosis virus which does not transform cells in vitro or carry an oncogene. When injected into 1-day-old hatched chicks, RAV-7 causes a low incidence of lymphoid leukosis after a latent period of several months. In contrast, infection of 10-day-old chicken embryos with RAV-7 leads to a disease syndrome characterized by stunting, obesity, atrophy of the bursa and the thymus, high triglyceride and cholesterol levels, reduced thyroxine levels, and increased insulin levels (Carter et al., Infect. Immun. 39:410-422, 1983; J. K. Carter and R. E. Smith, Infect. Immun. 40:795-805, 1983). Histopathological examination of tissues from affected chicks revealed an accumulation of lipid in the liver and an extensive infiltration of the thyroid and pancreas by lymphoblastoid cells. In the present investigation, the subgroup specificity of this syndrome was investigated. Other subgroup C avian leukosis viruses (transformation-defective B77, transformation-defective Prague C strain of Rous sarcoma virus, and RAV-49) caused stunting, infiltration of the thyroid and pancreas, increased liver weights, decreased thyroxine levels, and increased insulin levels, but they did not cause a uniform, profound increase in triglyceride and cholesterol levels. Avian leukosis viruses of subgroup A {myeloblastosis-associated virus 1