New Perspective on the Geographic Distribution and Evolution of Lymphocytic Choriomeningitis Virus, Central Europe

Abstract

Lymphocytic choriomeningitis virus (LCMV) is an Old World mammarenavirus found worldwide because of its association with the house mouse. When LCMV spills over to immunocompetent humans, the virus can cause aseptic meningitis; in immunocompromised persons, systemic infection and death can occur. Central Europe is a strategic location for the study of LCMV evolutionary history and host specificity because of the presence of a hybrid zone (genetic barrier) between 2 house mouse subspecies, Mus musculus musculus and M. musculus domesticus. We report LCMV prevalence in natural mouse populations from a Czech Republic-Germany transect and genomic characterization of 2 new LCMV variants from the Czech Republic. We demonstrate that the main division in the LCMV phylogenetic tree corresponds to mouse host subspecies and, when the virus is found in human hosts, the mouse subspecies found at the spillover location. Therefore, LCMV strains infecting humans can be predicted by the genetic structure of house mice.

Keywords: Czech Republic; Germany; Mus musculus domesticus; Mus musculus musculus; central Europe; lymphocytic choriomeningitis virus; viruses; zoonoses.

Figure 1

Worldwide distribution of Mus musculus mouse subspecies. Colors indicate subspecies ranges: green and tan, M. musculus castaneus; blue and purple, M. musculus domesticus; pink, M. musculus musculus ; gray, central populations and M. musculus gentilulus. Note that house mice may not be found throughout the complete extent of some areas (e.g., subarctic regions, the Sahara Desert, and the Amazon rainforest). The purple, and gray areas indicate regions of hybridization. Red arrows indicate inferred routes of historical migrations and recent movements in association with humans. Adapted from (7,8). Copyright ©2012 Springer-Verlag. All rights reserved. Adapted with permission from Springer Science and Business Media and Michael Nachman.

Figure 2

Tested localities for LCMV, Central Europe. The center of the HMHZ is represented by the orange line. The green rectangle n the inset map shows the sampling area, located in the center of the HMHZ. HMHZ, house mouse hybrid zone; LCMV, lymphocytic choriomeningitis virus.

Figure 3

Phylogenetic analysis performed on nucleic acid sequences of large gene of lymphocytic choriomeningitis virus (LCMV) sequences using Bayesian inference. Bayesian posterior probabilities were used to assess node support. Lunk virus from Mus minutoides (Africa) was used as outgroup. All sequences obtained in this study were submitted to GenBank (accession nos. MZ568450–7, MZ558311–3, MZ568449). Names of LCMV strains are composed of GenBank accession number, strain name, host species, and place and country of origin (if known) or isolation. Country code is defined as ISO code (https://countrycode.org). Colors indicate LCMV strains isolated from wild rodents where there is a match between expected mouse subspecies on the basis of geographic region and sampling area: blue, Mus musculus domesticus; red, M. musculus musculus. Arrows indicate known origin of mice subspecies on the basis of genetic data, asterisks (*) indicate LCMV strains from this study, and lineages are indicated by roman numerals. Scale bar indicates nucleotide substitutions per site. Mmd, M. musculus domesticus; Mmm, M. musculus musculus; Mmm_lab, laboratory mouse strain derived from M. musculus musculus; Mm_lab, laboratory mouse strain; Mm_sp, Mus musculus spp.

Figure 4

Phylogenetic analysis performed on nucleic acid sequences of glycoprotein gene of lymphocytic choriomeningitis virus (LCMV) sequences using Bayesian inference. Bayesian posterior probabilities were used to assess node support. Lunk virus from Mus minutoides (Africa) was used as outgroup. All sequences obtained in this study were submitted to GenBank (accession nos. MZ568450–7, MZ558311–3, MZ568449). Names of LCMV strains are composed of GenBank accession number, strain name, host species, and place and country of origin (if known) or isolation. Country code is defined as ISO code (https://countrycode.org). Colors indicate LCMV strains isolated from wild rodents where there is a match between expected mouse subspecies on the basis of geographic region and sampling area: blue, Mus musculus domesticus; red, M. musculus musculus. Arrows indicate known origin of mouse subspecies on the basis of genetic data, asterisks (*) indicates LCMV strains from this study, and lineages are indicated by roman numerals. LCMV strains isolated from Apodemus sylvaticus are indicated in green (lineage IV). Scale bar indicates nucleotide substitutions per site. Mmd, M. musculus domesticus; Mmm, M. musculus musculus; Mmm_lab, laboratory mouse strain derived from M. musculus musculus; Mm_lab, laboratory mouse strain; Mm_sp, Mus musculus spp.

Figure 5

Phylogenetic analysis performed on nucleic acid sequences of nucleoprotein gene of lymphocytic choriomeningitis virus (LCMV) sequences using Bayesian inference. Bayesian posterior probabilities were used to assess node support. Lunk virus from Mus minutoides (Africa) was used as outgroup. All sequences obtained in this study were submitted to GenBank (accession numbers: MZ568450–7, MZ558311–3, MZ568449). Names of LCMV strains are composed of GenBank number, strain name, host species, and place and country of origin (if known) or isolation. Country code is defined as ISO code (https://countrycode.org). Colors indicate LCMV strains isolated from wild rodents where there is a match between expected mouse subspecies on the basis of geographic region and sampling area: blue, Mus musculus domesticus; red, M. musculus musculus. Arrows indicate known origin of mice subspecies on the basis of genetic data, asterix indicates LCMV strains from this study, and lineages are indicated by roman numerals. LCMV strains isolated from Apodemus sylvaticus are indicated in green (lineage IV). Scale bar indicates nucleotide substitutions per site. Mmd, M. musculus domesticus; Mmm, M. musculus musculus; Mmm_lab, laboratory mouse strain derived from M. musculus musculus; Mm_lab, laboratory mouse strain; Mm_sp, Mus musculus spp.