Drosophila immunity and homeostasis during viral infection
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AbstractInsects are vectors for human disease and also play a critical role in agriculture. Like humans, insects encounter pathogens such as viruses. Despite having a profound impact on our lives, much has yet to be discovered about how insects respond to viral infection. All organisms have two options when under threat: disease resistance mechanisms and disease tolerance mechanisms. Disease resistance mechanisms are strategies to limit pathogen replication. For insects responding to a viral infection, RNA interference, Toll signaling, IMD signaling, autophagy, and Jak/STAT signaling have been identified as relevant immune mechanisms for restricting pathogen growth. However, each of these mechanisms has been studied to a varying extent, and the relative contribution of each to antiviral immunity has yet to be fully evaluated. The other option that infected insects have is to employ disease tolerance mechanisms. These strategies seek to maintain homeostasis and limit pathology when the animal undergoes stresses such as viral infection without necessarily limiting pathogen replication. Disease tolerance in animals is a nascent field of research, and the few existing experimental systems modeling disease tolerance prove challenging to study. Here, we employ Drosophila melanogaster as a genetically tractable model organism to study disease resistance and disease tolerance mechanisms in the context of viral infection. In vitro and in vivo infections were utilized to evaluate the relative contribution of antiviral resistance mechanisms. RNA interference was found to be the main contributor to antiviral immunity. Additionally, a gene orthologous to STING, a mediator of mammalian antiviral immunity, was found to have antiviral properties in fruit flies. A model for studying disease tolerance was also established. Vesicular stomatitis virus infection renders flies susceptible to coordinative defects only after carbon dioxide exposure, despite being otherwise asymptomatic. We found that the viral glycoprotein alone sufficiently abrogates the ability of flies to tolerate the stress of carbon dioxide anesthesia. The glycoprotein mediates syncytia formation in the nervous system, resulting in instantaneous pathology with ensuing morbidity. The data reported here demonstrate that disease resistance and tolerance mechanisms support the ability of insects to thrive in the face of pathogenic onslaughts.
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