RESUMO
Pathogen virulence is highly variable within populations, and although many factors contributing to virulence differences are known, there is still much variation left unexplained. Identifying and characterizing environmental conditions associated with different virulence levels is therefore an important undertaking in infectious disease research. One factor considered to be a major determinant of overall health and susceptibility to disease in social animals is social status. Health differences associated with social status are thought to be caused by different levels of chronic stress in higher- versus lower-status individuals. There is considerable evidence that these effects extend to the standing immune profile and that social status directly influences susceptibility to pathogens. Here we examined the association between dominance status in male wild-derived house mice, Mus musculus, and susceptibility to Friend virus complex in the context of seminatural populations with intense male-male competition and no predation. Due to an interruption in our facility's heating system, we were unexpectedly presented with the opportunity to assess how reduced ambient temperature influences the association of host social status and pathogen virulence. Environmental temperature has been implicated as a contributor to pathogen virulence, giving us a unique chance to examine its role in a previously unexamined pathogen system, while the added context of social status can expand our understanding of how the interaction of different environmental conditions affects virulence. We found that pathogen virulence and replication were lower in socially dominant hosts compared to nondominant hosts. When temperature was reduced, cool enclosure-housed dominant males were more susceptible to infection than their warm enclosure-housed counterparts. The mechanistic underpinnings that link infectious disease and social status remain difficult to disentangle from their associated factors, but this study opens the door for future experiments using a novel approach in the most well-studied mammalian model available.
RESUMO
Experimental evolution (serial passage) of Friend virus complex (FVC) in mice demonstrates phenotypic adaptation to specific host major histocompatibility complex (MHC) genotypes. These evolved viral lines show increased fitness and virulence in their host-genotype-of-passage, but display fitness and virulence tradeoffs when infecting unfamiliar host MHC genotypes. Here, we deep sequence these viral lines in an attempt to discover the genetic basis of FVC adaptation. The principal prediction for genotype-specific adaptation is that unique mutations would rise to high frequency in viral lines adapted to each host MHC genotype. This prediction was not supported by our sequencing data as most observed high-frequency variants were present in each of our independently evolved viral lines. However, using a multi-variate approach to measure divergence between viral populations, we show that populations of replicate evolved viral lines from the same MHC congenic mouse strain were more similar to one another than to lines derived from different MHC congenic mouse strains, suggesting that MHC genotype does predictably act on viral evolution in our model. Sequence analysis also revealed rampant recombination with endogenous murine leukemia virus sequences (EnMuLVs) that are encoded within the BALB/c mouse genome. The highest frequency variants in all six lines contained a 12 bp insertion from a recombinant EnMuLV source, suggesting such recombinants were either being favored by selection or were contained in a recombinational hotspot. Interestingly, they did not reach fixation, as if they are low fitness. The amount of background mutations linked to FVC/EnMuLV variable sites indicated that FVC/EnMuLV recombinants had not reached mutation selection equilibrium and thus, that EnMuLV sequences are likely continuously introgressing into the replicating viral population. These discoveries raise the question: is the expression of EnMuLV sequences in mouse splenocytes that permit recombination with exogenous FVC a pathogen or host adaptation?