Activation of the cellular oncogene c-erbB by LTR insertion: molecular basis for induction of erythroblastosis by avian leukosis virus.
Avian leukosis virus (ALV), a slowly oncogenic retrovirus, induces in chickens a variety of neoplasms, including lymphoid leukosis and erythroblastosis. In lymphoid leukosis, a cellular oncogene, c-myc, is activated by the insertion of ALV LTR. We provide evidence that ALV utilizes a similar mechanism in erythroblastosis induction by activating a different cellular oncogene, c-erbB. We report the isolation, from leukemic erythroblast DNA, of a clone that represents the viral-cell junction fragment and carried the ALV LTR and part of the c-erbB locus. Restriction and sequence analyses reveal that the LTR is located upstream from the erbB coding region and is oriented in the same transcriptional direction; such a structure would be compatible with the promoter-insertion type of activation. Our findings provide a molecular explanation for the multipotency of slowly oncogenic retroviruses.
D000818:Animals; D001353:Avian Leukosis / Q000235:genetics*; D001354:Avian Leukosis Virus / Q000235:genetics*; D001483:Base Sequence; D002645:Chickens; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004279:DNA, Viral / Q000502:physiology*; D015246:Deoxyribonuclease EcoRI; D009857:Oncogenes; D009876:Operon; D011201:Poultry Diseases / Q000235:genetics*
D004279:DNA, Viral; D004262:DNA Restriction Enzymes; D015246:Deoxyribonuclease EcoRI