Genomic analysis and pathogenic characteristics of lymphocytic choriomeningitis virus strains isolated in Japan

Area of Science:

• Virology
• Immunology
• Genomics

Background:

• Lymphocytic choriomeningitis virus (LCMV) is a zoonotic pathogen with mice as its natural reservoir.
• LCMV strains exhibit varying degrees of pathogenicity in mouse models.
• Understanding LCMV genetic diversity is crucial for assessing disease risk.

Purpose of the Study:

• To determine the complete genomic sequences of three LCMV strains: OQ28, BRC, and WE(ngs).
• To analyze the phylogenetic relationships of these LCMV strains.
• To evaluate the pathogenicity of these LCMV strains in a mouse model.

Main Methods:

• Complete genomic sequencing of LCMV strains OQ28, BRC, and WE(ngs).
• Phylogenetic analysis to determine genetic relatedness.
• Inoculation of ICR mice with different LCMV doses (10² and 10⁴ TCID₅₀) to assess pathogenicity.
• Clinical observation and viral load detection in blood and organs.

Main Results:

• Strains OQ28 and BRC showed high sequence homology with other LCMV strains and clustered together phylogenetically.
• WE(ngs) shared significant sequence substitutions with its parent strain WE but remained in the same subcluster.
• Mice infected with OQ28 or WE(ngs) displayed severe symptoms and mortality, while BRC infection caused no clinical signs or death.
• Viral detection was high in OQ28 and WE(ngs) infected mice, but negligible in BRC survivors.

Conclusions:

• LCMV strains OQ28 and BRC, despite belonging to the same genetic cluster, exhibit markedly different pathogenic potentials.
• Genomic analysis alone may not fully predict the pathogenicity of LCMV strains.
• Further research is needed to understand the molecular mechanisms underlying LCMV pathogenicity differences.