ABSTRACTUnderstanding viral dynamics in arthropods is of great importance when designing models to describe how viral spread can influence arthropod populations. The endosymbiotic bacteriumWolbachiaspp., which is present in up to 40% of all insect species, has the ability to alter viral dynamics in bothDrosophilaspp. and mosquitoes, a feature that in mosquitoes may be utilized to limit spread of important arboviruses. To understand the potential effect ofWolbachiaon viral dynamics in nature, it is important to consider the impact of natural routes of virus infection onWolbachiaantiviral effects. Using adultDrosophilastrains, we show here thatDrosophila-Wolbachiaassociations that have previously been shown to confer antiviral protection following systemic viral infection also confer protection against virus-induced mortality following oral exposure to Drosophila C virus in adults. Interestingly, a different pattern was observed when the same fly lines were challenged with the virus when still larvae. Analysis of the fourDrosophila-Wolbachiaassociations that were protective in adults indicated that only the w1118-wMelPop association conferred protection in larvae following oral delivery of the virus. Analysis ofWolbachiadensity using quantitative PCR (qPCR) showed that a highWolbachiadensity was congruent with antiviral protection in both adults and larvae. This study indicates thatWolbachia-mediated protection may vary between larval and adult stages of a givenWolbachia-host combination and that the variations in susceptibility by life stage correspond withWolbachiadensity. The differences in the outcome of virus infection are likely to influence viral dynamics inWolbachia-infected insect populations in nature and could also have important implications for the transmission of arboviruses in mosquito populations.