MHC class II DRB diversity in raccoons (Procyon lotor) reveals associations with raccoon rabies virus (Lyssavirus)

Abstract

In North America, the raccoon rabies virus (RRV) is an endemic wildlife disease which causes acute encephalopathies and is a strong selective force on raccoons (Procyon lotor), with estimates of ∼85% of the population succumbing to the disease when epizootic. RRV is regarded as a lethal disease if untreated; therefore, no evolutionary response would be expected of raccoon populations. However, variable immune responses to RRV have been observed in raccoons indicating a potential for evolutionary adaptation. Studies of variation within the immunologically important major histocompatibility complex (MHC) have revealed relationships between MHC alleles and diseases in humans and other wildlife species. This enhances our understanding of how hosts and pathogens adapt and co-evolve. In this study, we used RRV as a model system to study host-pathogen interaction in raccoons from a challenge study and from four wild populations that differ in exposure times and viral lineages. We investigated the potential role of Prlo-DRB polymorphism in relation to susceptibility/resistance to RRV in 113 RRV positive and 143 RRV negative raccoons. Six alleles were found to be associated with RRV negative status and five alleles with RRV positive animals. We found variable patterns of MHC associations given the relative number of selective RRV sweeps in the studied regions and correlations between MHC diversity and RRV lineages. The allelic associations established provide insight into how the genetic variation of raccoons may affect the disease outcome and this can be used to examine similar associations between other rabies variants and their hosts.

Extensive variation at MHC DRB in the New Zealand sea lion (Phocarctos hookeri) provides evidence for balancing selection

“…The detection of 28 nucleotide sequences that corresponded to 26 DRB peptides in 87 NZSL pups, three peptides of which account for the majority of observed alleles, is consistent with observations in terrestrial mammalian species (Schaschl et al, 2004;Becker et al, 2009;Srithayakumar et al, 2011). In fact, the detection of extensive variation at MHC DRB in mammalian species that are not of conservation concern is common; primates especially are highly variable at DRB (Otting et al, 2000;Schwensow et al, 2007).…”

Host–parasite network structure is associated with community-level immunogenetic diversity

“…At the individual host level, susceptibility to helminths can result from one of the two alleles or from a co-dominant effect of both, also depending on the parasite in question 13 . It is common in studies of MHC diversity to use only alleles/supertypes, rather than genotypes in statistical analyses 5,6,44 . However, owing to the lack of knowledge of the genetic mechanism, and because working with genotypes would create sparse networks, we used supertypes and validated our analyses with genotypes 13 .…”

“…These genes encode cellsurface glycoproteins that recognize and present foreign antigens, such as those of invading parasites, to T lymphocytes thereby initiating an immune response 4 . Thus, at the host individual level, certain MHC alleles confer resistance/susceptibility to some parasites but not to others [5][6][7] .…”

Major Histocompatibility Complex, demographic, and environmental predictors of antibody presence in a free-ranging mammal

“…Polymorphism primarily occurs in the antigen binding sites, also referred to as the peptide binding region (PBR), which are directly involved in antigen recognition (Hughes and Nei, 1988). High levels of polymorphism are mainly maintained by pathogen-mediated selection (Bernatchez and Landry, 2003;Piertney and Oliver, 2006) and variation at MHC has been linked to susceptibility (the risk of infection) and resistance (the ability to survive after exposure) for a wide range of pathogenic and host taxa (Hill, 1991;Grimholt et al, 2003;Harf and Sommer, 2005;Kloch et al, 2010;Savage and Zamudio, 2011;Srithayakumar et al, 2011).…”

“…We focus on free-ranging populations of raccoons (Procyon lotor) in Missouri, USA, where virtually all individuals (>80% of adults) are eventually exposed to both CDV and parvovirus . We analyzed the MHC II DRB exon 2 because it is highly polymorphic, is subject to natural selection (Castillo et al, 2010), and has been linked to rabies resistance and susceptibility in raccoons (Srithayakumar et al, 2011) and to CDV and canine parvovirus resistance in wolves (Hedrick et al, 2003). We tested whether the probability of individuals mounting a successful immune response (i.e.…”