Functional variation at an expressed MHC class II? locus predicts Ranavirus infection intensity in larval anuran populations

Abstract/Summary

Infectious diseases are causing catastrophic losses to global biodiversity. Iridoviruses in the genus Ranavirus are among the leading causes of amphibian disease-related mortality. Polymorphisms in major histocompatibility complex (MHC) genes are significantly associated with variation in amphibian pathogen susceptibility. MHC genes encode two classes of polymorphic cell-surface molecules that can recognize and bind to diverse pathogen peptides. While MHC class I genes are the classic mediators of viral acquired immunity, larval amphibians do not express them. Consequently, MHC class II gene diversity may be an important predictor of Ranavirus susceptibility in larval amphibians, the life stage most susceptible to Ranavirus. We surveyed natural populations of larval wood frogs (Rana sylvatica), which are highly susceptible to Ranavirus, across 17 ponds and two years in Maryland, USA. We sequenced the peptide-binding region of an expressed MHC class II? locus and assessed allelic and genetic diversity. We converted alleles to functional supertypes and determined if supertypes influenced host responses to Ranavirus. Among 384 sampled individuals, 26% were infected with Ranavirus. We recovered 20 unique MHC class II? alleles that fell into two deeply diverged clades and seven supertypes. MHC genotypes were associated with Ranavirus infection intensity, but not prevalence. Specifically, heterozygotes and individuals with genotype ST1/ST7 had significantly lower Ranavirus infection intensity compared to homozygotes and all other genotypes. We conclude that MHC class II? functional genetic variation is an important component of Ranavirus susceptibility. Identifying immunogenetic signatures linked to variation in disease susceptibility can inform mitigation strategies for combatting global amphibian declines.

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