POSSIBLE ORIGIN OF MURINE AIDS (MAIDS) VIRUS - CONVERSION OF AN ENDOGENOUS RETROVIRAL P12(GAG) SEQUENCE TO A MAIDS-INDUCING SEQUENCE BY FRAMESHIFT MUTATIONS

The murine AIDS (MAIDS) virus has a unique sequence in its p12(gag) re gion, which is responsible for MAIDS development. A transcript hybridi zing with this sequence is expressed in normal C57BL/6 mice. The trans cript, designated Edv, has been previously cloned and sequenced (Y. Ku bo, Y. Nakagawa, K. Kakimi, H. Matsui, K. Higo, L. Wang, H. Kobayashi, T. Hirama, and A. Ishimoto, J. Gen. Virol, 75:881-888, 1991). Compare d with the nucleotide sequence of the helper LP-BM5 ecotropic virus, t he pathogenic replication-defective MAIDS virus has a 16-bp deletion a nd a 1-bp insertion in the 5' and 3' regions of the p12(gag) sequence, respectively, and the Edv transcript contains only a 3-bp deletion. T herefore, the amino acid sequence of the defective MAIDS virus p12(gag ) region is not homologous to that of the helper virus and the Edv tra nscript because of the frameshift. To determine whether the amino acid sequence resulting from the frameshift is critical for MAIDS developm ent, we constructed chimeric viruses that contained the p12(gag) regio ns of the helper virus and the Edv transcript, respectively, with and without the same frame as the defective MAIDS virus by the artificial frameshift mutations. The mutant viruses with the frameshift mutations induced MAIDS in inoculated mice, but the viruses without the mutatio ns did not. These results suggested that the MAIDS virus was generated by frameshift mutations in the p12(gag) region of Edv or a related se quence.