Defense strategies against pathogens can be categorized into disease resistance, the host mechanisms involved in the reduction of pathogen, or disease tolerance, where hosts do not exert a direct impact on pathogens but instead limit its cost on health and fitness.
In Drosophila melanogaster, genetic variation in mortality following infection with Drosophila C virus (DCV) is driven by large effect polymorphisms in the restriction factor pastrel (pst). However, it is unclear if pst contributes to disease tolerance.
In this work, we described genetic variation in disease tolerance using flies carrying either a susceptible (S) or resistant (R) pst allele, across a range of DCV doses. We found 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). Besides, we found that the pst gene is associated with general vigour in the absence of infection and confirm its role in reducing DCV titres during infection.
For this paper, co-led by Megan Kutzer and Vanika Gupta, Kyriaki Neophytou and myself analyzed gene expression variations across fly lines, and showed pst affects the expression of genes involved in disease tolerance, namely upd3 and G9a.
This work represents one of the first descriptions of genetic variation in mortality tolerance and fecundity tolerance in a viral infection of invertebrates.
The reference:
Kutzer MAM, Gupta V, Neophytou K, Doublet V, Monteith KM, Vale PF (2023) Intraspecific genetic variation in host vigour, viral load and disease tolerance during Drosophila C virus infection. Open Biology. 13:230025. https://doi.org/10.1098/rsob.230025
And the journal cover:
Vincent Doublet 