At least two regions of the viral genome determine the oncogenic potential of avian leukosis viruses.

Abstract

Recombinants of oncogenic and nononcogenic avian leukosis viruses were tested for their oncogenic potential in chickens. The results indicate that at least two regions of the viral genome determine the oncogenic potential of these viruses. The first region contains sequences that control viral mRNA synthesis. These sequences determine the potential of a virus to induce a low incidence oflymphomas, carcinomas, chondrosarcomas, fibrosarcomas, and osteopetrosis. The second region lies outside the sequences that control viral mRNA synthesis. These sequences determine the ability of a virus to induce a high incidence of lymphomas or osteopetrosis.

Enhancer activity correlates with the oncogenic potential of avian retroviruses.

“…In fact, RAV-0 becomes oncogenic when its own U3 region is replaced by that of RSV (Robinson et al, 1982;Tsichlis et al, 1982). Furthermore, it has been demonstrated that the LTR of a tumorigenic retrovirus (RAV-2) gives rise to a 10-fold higher level of env gene transcription than the RAV-0 LTR (Cullen et al, 1983).…”

“…Since RAV-0 is an endogenous virus which also has the ability to multiply in avian cells, it might be that the loss of enhancer activity evolved to reduce oncogenicity without losing viability. Robinson et al (1982) and Tsichlis et al (1982) have demonstrated that replacing the U3 region of the RAV-0 LTR with the homologous region of td-RSV restores oncogenicity in vivo. Thus, the U3 region determines the potential of a virus to induce malignant diseases such as lymphomas, carcinomas, chondrosarcomas, fibrosarcomas and osteopetrosis Robinson et al, 1982).…”

“…Robinson et al (1982) and Tsichlis et al (1982) have demonstrated that replacing the U3 region of the RAV-0 LTR with the homologous region of td-RSV restores oncogenicity in vivo. Thus, the U3 region determines the potential of a virus to induce malignant diseases such as lymphomas, carcinomas, chondrosarcomas, fibrosarcomas and osteopetrosis Robinson et al, 1982). Additional viral sequences determine the relative frequency of particular tumors and may be responsible for specific targeting of the virus (Robinson et al, 1982).…”

“…Detailed comparison of RAV-0 and RSV by restriction analysis and sequencing has revealed clear differences in the U3 region of the long terminal repeats (LTRs) and only minor differences in other parts of the viral genomes (Hughes, 1982;Robinson et al, 1982). In fact, RAV-0 becomes oncogenic when its own U3 region is replaced by that of RSV (Robinson et al, 1982;Tsichlis et al, 1982).…”

Genetic mapping of a cellular DNA region involved in induction of thymic lymphomas (Mlvi-1) to mouse chromosome 15.

“…Alternatively, oncogene activation and neoplastic disease can also follow the chromosomal integration of a nonacute transforming retrovirus near these potentially transforming host genes. The major retroviral sequences necessary for transformation in avian leukosis virus have been localized to the U3 region of retroviral long terminal repeats (LTRs) (21,22,(31)(32)(33). Recent studies with murine nontransforming retroviruses also argue for the importance of the proviral LTR sequences in determining oncogenicity (3,6,15).…”