Genome sequencing of reassortants of zoonotic lymphocytic choriomeningitis virus
Lymphocytic choriomeningitis virus (LCMV) is a neglected zoonotic mammalian arenavirus primarily transmitted by house mice (Mus musculus). In humans, LCMV infection can cause encephalitis or meningitis, severe birth defects in prenatal infections. In addition, LCMV causes acute and fatal callitrichid hepatitis (CH) in New World (NW) primates. Following the detection of LCMV lineages I and II in wild house mice in a zoological garden in Germany, here, we investigate the persistence and evolution of LCMV lineages in the population and retrospective spill-over infections. Continued monitoring revealed an increasing prevalence of both lineages I and II in this wild house mouse population but only lineage II spill-over to captive primates. Estimation of the time to the most recent ancestor, combined with the detection of lineage II in retrospective NW primate samples from 2014, suggest that its incursion into the zoological garden occurred between 2010 and 2014. Furthermore, mtDNA, autosomal, and Y-chromosomal assignment of house mice from the zoological garden confirm that house mice from 2009 and 2023 are Mus musculus domesticus. Lineage-specific RT-qPCR, Sanger and next-generation sequencing, virus isolation and limiting dilution, we were able to confirm the co-occurrence of both lineages is accompanied by co-infections and the emergence of reassortant viruses. The isolated viral reassortants (N=3) in this study all contained an S-segment of lineage II and an L-segment of lineage I. While the evolutionary benefits of this reassortment event remain unclear, potential variations in spillover capability and pathogenicity among these viral strains could lead to distinct epidemiological patterns. In conclusion, the continued presence of two distinct LCMV lineages within this house mouse population provides a unique opportunity to advance our understanding of arenavirus evolutionary dynamics, but may also poses a significant potential public health threat for human and NW primates by facilitating the emergence of novel LCMV strains. Further viral characterization is needed to assess potential phenotypic differences among reassortants and the underlying mechanisms driving their production.