Complete nucleotide sequence of the neurotropic murine retrovirus CAS-BR-E.

Neurotropic murine retroviruses were isolated from a population of wild mice by Gardner et al. (1). These viruses have an ecotropic host range and cause, after neonatal inoculation, a noninflammatory neurodegenerative disease characterized by spongiform degeneration primarily localized to motor areas of the brain stem and spinal cord (2). The major determinant of neurovirulence has been mapped to the viral envelope gene (3), but both the U3 region of the LTR (4) and 5' untranslated region (5) of the viral genome exclusive of U3 affect both the tempo and character of the disease. The Cas-Br-E clone (15 — 1) containing the entire viral genome was ligated into the vector pUC 19 at the Sail site within the pol gene (base 3698 of the given sequence) (6). Sequence data was obtained on double-stranded plasmid DNA using the dideoxy chain-termination method with E. coli DNA polymerase, Klenow fragment, and labeled with a-S-dATP. Specific primers for sequencing were synthesized on an Applied Biosystems 380B DNA synthesizer. The sequence of the env, 3' pol genes and the LTR was previously published by Rassart et al. (7) using a different molecular clone (pBRNE8) of Cas-Br-E. There were only two amino acid differences in env and one amino acid difference in 3' pol between the predicted translation products of Cas-Br-E clones 15-1 and pBRNES. At the nucleic acid level there were 5 discrepancies in the LTR, 5 in env and 2 in the 3' end of pol. The level of homology between Cas-Br-E clone 15-1 and two other murine leukemia viruses which have been completely sequenced, is presented in the table below. Table: Sequence homology between Cas-Br-E clone 15-1 and other MuLV's