STUDIES ON THE ANTIGENICITY AND NUCLEOTIDE-SEQUENCE OF THE RABIES VIRUS NISHIGAHARA STRAIN, A CURRENT SEED STRAIN USED FOR DOG VACCINE PRODUCTION IN JAPAN

The Nishigahara strain of rabies virus, a current seed strain used for animal vaccine production in Japan, is believed to derive from the or iginal Pasteur strain obtained from Paris in or before 1915. In Japan, the virus was serially passaged through several kinds of animals and cell cultures. Reactions with anti-nucleocapsid protein monoclonal ant ibodies (MAb-N) indicated the Nishigahara strain had maintained the an tigenic profile of the Pasteur virus. Reactions with monoclonal antibo dies to the glycoprotein (MAb-G) revealed differences between the Nish igahara strain and the Pasteur strain; however, the Nishigahara strain maintained a closer resemblance to the Pasteur virus than to other Pa steur-related viruses or to rabies strains unrelated to the Pasteur st rain. Comparative amino acid sequence analysis of cloned cDNA encoding the G gene confirmed the antigenic differences among these strains an d the resemblance of the Nishigahara strain to the original Pasteur st rain. Comparative nucleotide sequence analysis of the noncoding pseudo gene region (Tordo et al., Proc Natl Acad Sci USA 83, 3914-3918, 1986) revealed different relationships. Unlike the Pasteur strain, which en codes a transcription-terminating signal at the end of the G gene (mar king the beginning of the pseudogene), a long G-L intergenic sequence in the Nishigahara strain was connected to the 3' end of the cDNA, and the transcription-terminating signal was present only at the end of, but not before, the pseudogene. These results are not inconsistent wit h the documented origin of the Nishigahara strain, but the genome stru cture around the pseudogene region suggests divergence from the Pasteu r strain and a closer resemblance to other strains of rabies virus.