The Fly Way of Antiviral Resistance and Disease Tolerance

Like humans, insects face the threat of viral infection. Despite having repercussions on human health and disease, knowledge gaps exist for how insects cope with viral pathogens. Drosophila melanogaster serves as an ideal insect model due to its genetic tractability. When encountering a pathogen, two major approaches to fight disease are resistance strategies and tolerance strategies. Disease resistance strategies promote the health of the infected host by reducing pathogen load. Multiple disease resistance mechanisms have been identified in Drosophila: RNA interference, Jak/STAT signaling, Toll signaling, IMD signaling, and autophagy. Disease tolerance mechanisms, in contrast, do not reduce pathogen load directly, but rather mitigate the stress and damage incurred by infection. The main benefit of tolerance mechanisms may therefore be to provide the host with time to engage antiviral resistance mechanisms that eliminate the threat. In this review, antiviral resistance mechanisms used by Drosophila will be described and compared to mammalian antiviral mechanisms. Disease tolerance will then be explained in a broader context as this is a burgeoning field of study.