Independent recombination between avian leukosis virus terminal sequences and host DNA in virus-induced proliferative disease.

A cDNA transcript of Rous sarcoma virus, which contained the long terminal repeat (LTR) and some additional 3'-terminal sequences, was inserted into the plasmid pBR322. This recombinant plasmid, p53, was then used as a hybridization probe to detect viral terminal sequences in DNA from a number of tissues of birds with a variety of avian leukosis virus (ALV)-induced proliferative diseases. Using restriction endonuclease digestion and blot hybridization analysis, we detected, in addition to standard ALV genomes, viral terminal sequences linked to host DNA and not to viral genes. In DNA from bursal lymphomas and nephroblastomas, we observed small numbers of integration sites occupied by sequences in p53 and lacking most or all of the remainder of the viral genome. In DNA from osteopetrosis, we observed apparently multiple copies of molecules containing host DNA linked to viral LTR sequences. Some of these structures were contained in discrete, probably unintegrated, DNA molecules. We concluded that viral LTR sequences can be inserted as independent elements during recombination with host DNA in some forms of interaction between exogenous retroviruses and host cells. Because the LTRs have been implicated in integration and transcription of viral genes, the possibility that translocation or activation, or both, of host genes may occur as a consequence of viral infection is reinforced by these observations.