Intraspecific genetic variation in host vigour, viral load and disease tolerance during Drosophila C virus infection.

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.