Department of Biology, University of Central Florida, 4110 Libra Drive, Orlando, FL, 32816, USA.
Center for Conservation Genomics, Smithsonian Conservation Biology Institute, National Zoological Park, 3001 Connecticut Avenue NW, Washington, DC, 20008, USA.
Immunogenetics. 2019 Apr;71(4):335-346. doi: 10.1007/s00251-019-01104-1. Epub 2019 Feb 13.
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 2 years in Maryland, USA. We sequenced the peptide-binding region of an expressed MHC class IIβ locus and assessed allelic and genetic diversity. We converted alleles to functional supertypes and determined if supertypes or alleles influenced host responses to Ranavirus. Among 381 sampled individuals, 26% were infected with Ranavirus. We recovered 20 unique MHC class IIβ alleles that fell into two deeply diverged clades and seven supertypes. MHC genotypes were associated with Ranavirus infection intensity, but not prevalence. Specifically, MHC heterozygotes and supertype ST1/ST7 had significantly lower Ranavirus infection intensity compared to homozygotes and other supertypes. We conclude that MHC class IIβ 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.
传染病正在给全球生物多样性造成灾难性的损失。虹彩病毒属的 Ranavirus 是导致与两栖动物疾病相关的死亡率的主要原因之一。主要组织相容性复合体 (MHC) 基因的多态性与两栖动物病原体易感性的变化显著相关。MHC 基因编码两类具有多态性的细胞表面分子，能够识别和结合多种病原体肽。虽然 MHC Ⅰ类基因是经典的病毒获得性免疫介质，但幼体两栖动物不表达它们。因此，MHC Ⅱ类基因多样性可能是幼体两栖动物对 Ranavirus 易感性的重要预测指标，幼体是最易受 Ranavirus 感染的生命阶段。我们在美国马里兰州的 17 个池塘和 2 年的时间里，对高度易受 Ranavirus 感染的幼体林蛙（Rana sylvatica）的自然种群进行了调查。我们对一个表达 MHC Ⅱβ基因座的肽结合区进行了测序，并评估了等位基因和遗传多样性。我们将等位基因转换为功能超型，并确定超型或等位基因是否影响宿主对 Ranavirus 的反应。在 381 名被采样的个体中，有 26%感染了 Ranavirus。我们共回收了 20 个独特的 MHC Ⅱβ等位基因，它们分为两个深度分化的分支和七个超型。MHC 基因型与 Ranavirus 感染强度有关，但与流行率无关。具体来说，MHC 杂合子和超型 ST1/ST7 与纯合子和其他超型相比，Ranavirus 感染强度显著降低。我们得出结论，MHC Ⅱβ功能遗传变异是 Ranavirus 易感性的一个重要组成部分。确定与疾病易感性变化相关的免疫遗传特征，可以为对抗全球两栖动物数量减少的策略提供信息。
