Genetic diversity among lassa virus strains

The arenavirus Lassa virus causes Lassa fever, a viral hemorrhagic fever th at is endemic in the countries of Nigeria, Sierra Leone, Liberia, and Guine a and perhaps elsewhere in West Africa. To determine the degree of genetic diversity among Lassa virus strains, partial nucleoprotein (NP) gene sequen ces mere obtained from 54 strains and analyzed. Phylogenetic analyses showe d that Lassa viruses comprise four lineages, three of which are found in Ni geria and the fourth in Guinea, Liberia, and Sierra Leone. Overall strain v ariation in the partial NP gene sequence was found to be as high as 27% at the nucleotide level and 15% at the amino acid level. Genetic distance amon g Lassa strains was found to correlate with geographic distance rather than time, and no evidence of a "molecular clock" was found. A method for ampli fying and cloning full-length arenavirus S RNAs was developed and used to o btain the complete NP and glycoprotein gene (GP1 and GP2) sequences for hvo representative Nigerian strains of Lassa virus. Comparison of full-length gene sequences for four Lassa virus strains representing the four lineages showed that the NP gene (up to 23.8% nucleotide difference and 12.0% amino acid difference) is more variable than the glycoprotein genes. Although the evolutionary order of descent within Lassa virus strains was not completel y resolved, the phylogenetic analyses of full-length NP, GP1, and GP2 gene sequences suggested that Nigerian strains of Lassa virus were ancestral to strains from Guinea, Liberia, and Sierra Leone, Compared to the New World a renaviruses, Lassa and the other Old World arenaviruses have either undergo ne a shorter period of diverisification or are evolving at a slower rate. T his study represents the first large-scale examination of Lassa virus genet ic variation.