MOLECULAR-CLONING AND CHARACTERIZATION OF A MURINE AIDS VIRUS-RELATEDENDOGENOUS TRANSCRIPT EXPRESSED IN C57BL 6 MICE/

The murine AIDS (MAIDS) virus has a unique sequence in the gag p12 reg ion, which could be responsible for MAIDS development. RNA preparation s from the spleens of normal uninfected C57BL/6 mice contain a transcr ipt hybridizing with this sequence. Levels of the transcript in the ki dney of C57BL/6 mice were higher than in the spleen, liver or thymus. Although BALB/c, NFS, DBA/2 and SL murine strains also contained genom ic sequences hybridizing with the MAIDS virus-specific probe, no trans cript hybridizing with the probe was detected in these strains of mice . The cDNAs carrying the transcript expressed in C57BL/6 mice were mol ecularly cloned. The complete nucleotide sequence of the clone indicat es that the transcript is one of the endogenous murine leukaemia virus -related sequences containing large deletions from the R and U5 region s of the 5' long terminal repeat (LTR) to gag p15, from the C-terminal region of pol p40 (integrase) to the N-terminal region of env p15E, a nd many short deletions in the 3' LTR U3 region. The nucleotide sequen ce in the gag p12 region of the transcript was closely similar to that of the MAIDS virus, but the amino acid sequence was less similar beca use of frameshifting, even when translated. As the MAIDS virus was iso lated from C57BL/6 mice with radiation-induced leukaemia, this transcr ipt may be the progenitor of the MAIDS virus. To determine whether; th e gag p12 region of the transcript contains a functional sequence, a r ecombinant virus was generated by replacing the gag p12 region of a re plication-competent BM5eco virus with that of the endogenous transcrip t. The recombinant virus was replication-competent, and the p12 region of the transcript retained the functional sequence present in the BM5 eco virus.