Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, UK.
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, UK.
Open Biol. 2023 Mar;13(3):230025. doi: 10.1098/rsob.230025. Epub 2023 Mar 1.
Genetic variation for resistance and disease tolerance has been described in a range of species. In , genetic variation in mortality following systemic Drosophila C virus (DCV) infection is driven by large-effect polymorphisms in the restriction factor . However, it is unclear if contributes to disease tolerance. We investigated systemic DCV challenges spanning nine orders of magnitude, in males and females of 10 Genetic Reference Panel lines carrying either a susceptible (S) or resistant (R) allele. We find among-line variation in fly survival, viral load and disease tolerance measured both as the ability to maintain survival (mortality tolerance) and reproduction (fecundity tolerance). We further uncover novel effects of on host vigour, as flies carrying the R allele exhibited higher survival and fecundity even in the absence of infection. Finally, we found significant genetic variation in the expression of the JAK-STAT ligand and the epigenetic regulator of JAK-STAT However, while has been previously shown to mediate tolerance of DCV infection, we found no correlation between the expression of either or on fly tolerance or resistance. Our work highlights the importance of both resistance and tolerance in viral defence.
遗传变异对抵抗和疾病耐受性的影响在多种物种中都有描述。在，系统果蝇 C 病毒（DCV）感染后死亡率的遗传变异是由限制因子中的大效应多态性驱动的。然而，目前尚不清楚是否有助于疾病耐受性。我们研究了跨越九个数量级的系统 DCV 挑战，涉及携带易感（S）或抗性（R）等位基因的 10 个遗传参考面板（Genetic Reference Panel，简称：GRP）线的雄性和雌性果蝇。我们发现，在不同品系的果蝇生存、病毒载量和疾病耐受性方面存在差异，这些差异既体现在维持生存（死亡率耐受性）的能力上，也体现在繁殖（繁殖力耐受性）方面。我们进一步揭示了 对宿主活力的新影响，因为携带 R 等位基因的果蝇即使在没有感染的情况下也表现出更高的存活率和繁殖力。最后，我们发现 JAK-STAT 配体 和 JAK-STAT 表观遗传调节剂 的表达存在显著的遗传变异。然而，尽管 先前被证明可以介导 DCV 感染的耐受性，但我们没有发现 或 的表达与果蝇的耐受性或抗性之间存在相关性。我们的工作强调了抵抗和耐受性在病毒防御中的重要性。
