An aberrant avian leukosis virus provirus inserted downstream from the chicken c-myc coding sequence in a bursal lymphoma results from intrachromosomal recombination between two proviruses and deletion of cellular DNA.
A chicken bursal lymphoma, LL6, contains avian leukosis virus DNA integrated 3' of the c-myc coding sequences, unlike all other examined bursal lymphomas, which have integrations 5' to c-myc. To better understand this unusual mutation, we examined a molecular clone containing the LL6 c-myc gene and determined the structure of the proviral insertion by DNA sequencing. Viral DNA begins 575 base pairs downstream of the c-myc coding sequences within the untranslated region, disrupting the use of the normal polyadenylation signal. An internal deletion of the provirus extends from within U3 in the 5' long terminal repeat to within the gp37-coding region of the env gene, disabling virus replication and protein synthesis. Both host-virus boundaries appear normal with respect to the site in viral DNA which is joined to host DNA; both long terminal repeats lack the terminal dinucleotide found in unintegrated DNA. However, in contrast to normal integrations, the six bases of cellular sequence at the 5' junction are not repeated at the 3' junction. The DNA sequences immediately downstream of the LL6 recombinant provirus are not part of the c-myc gene; they originate from the same chromosome as c-myc, but at least 15 kilobases (kb) away. In addition, DNA sequences normally residing 3' of c-myc are deleted in LL6. In summary, these results imply that the LL6 provirus is the result of recombination between two proviruses; that both proviruses were originally downstream of c-myc in the same orientation and separated by at least 15 kb; and that the recombination event was preceded, accompanied, or followed by an internal proviral deletion. No transcript could be detected within a 20-kb region downstream of the LL6 provirus, leaving unresolved the question of whether the additional chromosomal alterations make a specific contribution to LL6 tumorigenesis.
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D001483:Base Sequence; D002645:Chickens; D002872:Chromosome Deletion; D004273:DNA, Neoplasm / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D005786:Gene Expression Regulation; D005814:Genes, Viral; D008223:Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011995:Recombination, Genetic
D004273:DNA, Neoplasm; D004279:DNA, Viral; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc