Phylogenetic and Mutational Analysis of Lassa Virus Strains Isolated in Nigeria: Proposal for an In Silico Study

JMIR Res Protoc. 2021 Mar 26;10(3):e23015. doi: 10.2196/23015.

Abstract

Background: In 2018, the total number of Lassa fever cases in Nigeria was significantly higher than that observed in previous years. Hence, studies had attempted to determine the underlying cause. However, reports using phylogenetic methods to analyze this finding ruled out the emergence of potentially more transmissible Lassa virus strains or an increase in human-to-human viral transmission as the cause underlying the increase in cases. Two years later, the situation seems even worse as the number of confirmed cases has reached an all-time high according to situational reports released by the Nigerian Center for Disease Control.

Objective: Considering the increasing trend of Lassa fever cases and related mortality, the major objective of this study is to map mutations within the genomes of Lassa virus isolates from 2018 and 2019 using the reference sequence available at the National Center for Biotechnology Information as a benchmark and compare them to the genomes of viruses isolated during 1969-2017. This study would also attempt to identify a viral marker gene for easier identification and grouping. Finally, the time-scaled evolution of Lassa virus in Nigeria will be reconstructed.

Methods: After collecting the sequence data of Lassa virus isolates, Bayesian phylogenetic trees, a sequence identity matrix, and a single nucleotide polymorphism matrix will be generated using BEAST (version 2.6.2), Base-By-Base, and DIVEIN (a web-based tool for variant calling), respectively.

Results: Mining and alignment of Lassa virus genome sequences have been completed, while mutational analysis and the reconstruction of time-scaled maximum clade credibility trees, congruence tests for inferred segments, and gene phylogeny analysis are ongoing.

Conclusions: The findings of this study would further the current knowledge of the evolutionary history of the Lassa virus in Nigeria and would document the mutations in Nigerian isolates from 1969 to 2019.

International registered report identifier (irrid): DERR1-10.2196/23015.

Keywords: Arenavirus; Bayesian phylogeny; Lassa virus; Mammarenavirus; Nigeria; epidemic; evolution; marker gene; molecular epidemiology; mutations.