Abstract

Objective: To study the virulence diversity through molecular evolution, and to provide insight on circulating antibodies. Methods: The nucleotide sequences of 18 Lassa virus genomic RNA encoding Lassa virus nucleoprotein isolates collected from different parts of the world since the identification of the Josiah strain were obtained from the GenBank and nucleotide substitution among them studied using the computer program MEGA 4. The genetic distances among strains were predicted by pairwise nucleotide differences. Results: The rate of synonymous substitution was high 5.889 per nucleotide per year and nonsynonymous was higher at 49.664. The average predicted rate of synonymous and nonsynonymous using modified Nei-Gojobori (assuming transition/transversion bias=2) was 27.9 which was taken as the genetic distance between strains. The average number of synonymous sites is 150.741 while the average number of nonsynonymous sites is 392.259. The phylogenetic tree was inferred by unweighted pairwise grouping in MEGA4 and using neighbour-joining method. The time of emergence of Lassa virus was predicted to be around January 1920. However, the first human appearance of the virus was predicted to be around May (1 959暲24) months. In synonymous substitution the rate of (G-T) rare was high. The nucleotide frequencies were 0.314 (A), 0.246 (T/U), 0.204 (C) and 0.235 (G). The transition/transversion ratio k1=14.991 (purines) and k2=69.916 (pyrimidines). The overall transition/transversion bias R=16.662 with a total of 620 position in the final data set. These figures are far higher than an earlier study using Lassa virus glycoprotein. The nucleotide diversity were also very high using the Taijima’s model in MEGA 4. Conclusions: The divergence within strains always coincides with the period of epidemic which goes to confirm that the cause of epidemic outbreak should be the emergence of new strain and also why the infection remains endemic despite circulating antibodies. A comparison with a similar study with the viral glycoprotein concludes that the glycoprotein is more suited for vaccine development.

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