Sequence comparison of the large genomic RNA segments of two strains of lymphocytic choriomeningitis virus differing in pathogenic potential for guinea pigs

Two strains of lymphocytic choriomeningitis virus (LCMV) differ in their ab ility to cause a lethal disease in outbred guinea pigs: the Armstrong (ARM) strain is not lethal at high doses (10(6) PFU), whereas the WE strain is l ethal at less than 10 PFU inoculated intraperitoneally. The high pathogenic potential of LCMV WE has been mapped to the larger (L) of the two genomic RNA segments by genetic reassortment analysis (Riviere, Y., Ahmed, R., Sout hern, P.J., Buchmeier, M. J. and Oldstone, M. B. A., J. Virol. 55, 704-709, 1985). Here we describe the completed sequence of the LCMV WE L RNA, and i ts comparison to the L RNA of the non-virulent strain, LCMV ARM. Similar to the L RNA of LCMVARM, the L RNA of WE is 7.2 kb long and contains two open reading frames (ORFs): the 5" ORF encodes a small RING finger (zinc-bindin g) protein, p11 Z, and the 3" ORF encodes the putative RNA-dependent RNA po lymerase (RdRp or L protein). Comparison of nucleotide sequences for both v iruses revealed 84% L RNA homology. At the amino acid level similarity betw een the two strains is 87% in the Z ORF, and 88% in the RdRp ORF. The most divergent regions are found in the N-terminal parts of the RdRp and Z prote ins and are most likely to account for differences in pathogenic potential.