Wolbachia -Conferred Antiviral Protection Is Determined by Developmental Temperature.

Wolbachia is a maternally transmitted bacterium that is widespread in arthropods and filarial nematodes and confers strong antiviral protection in Drosophila melanogaster and other arthropods. Wolbachia -transinfected Aedes aegypti mosquitoes are currently being deployed to fight transmission of dengue and Zika viruses. However, the mechanism of antiviral protection and the factors influencing are still not fully understood. Here, we show that temperature modulates Wolbachia -conferred protection in Drosophila melanogaster. Temperature after infection directly impacts Drosophila C virus (DCV) replication and modulates Wolbachia protection. At higher temperatures, viruses proliferate more and are more lethal, while Wolbachia confers lower protection. Strikingly, host developmental temperature is a determinant of Wolbachia -conferred antiviral protection. While there is strong protection when flies develop from egg to adult at 25°C, the protection is highly reduced or abolished when flies develop at 18°C. However, Wolbachia -induced changes during development are not sufficient to limit virus-induced mortality, as Wolbachia is still required to be present in adults at the time of infection. This developmental effect is general, since it was present in different host genotypes, Wolbachia variants, and upon infection with different viruses. Overall, we show that Wolbachia -conferred antiviral protection is temperature dependent, being present or absent depending on the environmental conditions. This interaction likely impacts Wolbachia -host interactions in nature and, as a result, frequencies of host and symbionts in different climates. Dependence of Wolbachia -mediated pathogen blocking on developmental temperature could be used to dissect the mechanistic bases of protection and influence the deployment of Wolbachia to prevent transmission of arboviruses. IMPORTANCE Insects are often infected with beneficial intracellular bacteria. The bacterium Wolbachia is extremely common in insects and can protect them from pathogenic viruses. This effect is being used to prevent transmission of dengue and Zika viruses by Wolbachia -infected mosquitoes. To understand the biology of insects in the wild, we need to discover which factors affect Wolbachia -conferred antiviral protection. Here, we show that the temperature at which insects develop from eggs to adults can determine the presence or absence of antiviral protection. The environment, therefore, strongly influences this insect-bacterium interaction. Our work may help to provide insights into the mechanism of viral blocking by Wolbachia , deepen our understanding of the geographical distribution of host and symbiont, and incentivize further research on the temperature dependence of Wolbachia- conferred protection for control of mosquito-borne disease.