Regional Lassa virus lineages select for divergent MHC-I repertoires in Mastomys natalensis rodents

Identifying genes under local adaptation is an essential step to understand the mechanisms of adaptive evolution. Pathogen-mediated selection is expected to enhance host fitness by favouring resistance to locally prevalent pathogens. However, such pathogen-driven adaptation has been documented in only a few natural systems. Here, we sequenced the Major Histocompatibility Complex Class I region (MHC-I) of 739 Mastomys natalensis captured in Guinea and Nigeria, where the rodent is reservoir to two distinct Lassa virus (LASV) lineages. As predicted, the MHC-I profiles of the two countries, while showing overlap, did not cluster together. Moreover, different MHC-I alleles were associated with active or past infection measured as PCR-positive or IgG-positive, respectively, in each population. MHC-I allele ManaMHC-I*017 showed a diametric response, with individuals carrying this allele less likely to be found with an ongoing LASV infection in Guinea while more likely in Nigeria. Similarly, individuals with ManaMHC-I*069 were less likely to have a positive antibody test in Guinea but the same allele had little effect on IgG detection in Nigeria, suggesting that an individual's fitness depends on its immunogenetic repertoire. Together, these findings encapsulate a genetically characterised case of local adaptation in a wild virus-rodent system. Moreover, we hypothesise that aside from differences in virus diversity, genetic variation within regional LASV lineages contributes to the marked differences in host immunogenetic diversity.