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Martins, N. E.

Publications and source records attributed to Martins, N. E..

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Wolbachia-conferred antiviral protection is determined by developmental temperature

Wolbachia is a maternally transmitted bacterium widespread in arthropods and filarial nematodes, and confers strong antiviral protection in Drosophila melanogaster and other insects. Wolbachia-transinfected Aedes aegypti are currently being deployed to fight transmission of dengue and Zika viruses. However, the mechanism of antiviral protection and factors influencing it 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 replication and modulates Wolbachia protection. At higher temperatures virus proliferates more and is more lethal, while Wolbachia confers lower protection. Strikingly, host developmental temperature is a determinant of Wolbachia-conferred antiviral protection. While there is a strong protection when flies are raised from egg to adult at 25{degrees}C, the protection is highly reduced or completely abolished when flies develop at 18{degrees}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 should be considered by programmes deploying Wolbachia as an antiviral agent in the field. Significance StatementInsects are often infected with beneficial intracellular bacteria. The bacterium Wolbachia can protect insects from pathogenic viruses. This effect can be used to prevent transmission of dengue and Zika viruses by Wolbachia-infected mosquitoes. To deploy Wolbachia in the field successfully and 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 in which insects develop from eggs to adults can determine presence or absence of antiviral protection. The environment, therefore, influences this insect-bacterium interaction. Our work may help to provide insights into the mechanism of viral blocking by Wolbachia and inform programs using Wolbachia in mosquito-borne disease control.

microbiology

2'3'-cGAMP triggers a STING and NF-κB dependent broad antiviral response in Drosophila

We recently reported that an orthologue of STING regulates infection by picorna-like viruses in drosophila. In mammals, STING is activated by the cyclic dinucleotide 23-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we show that injection of flies with 23-cGAMP can induce expression of dSTING-regulated genes. Co-injection of 23-cGAMP with a panel of RNA or DNA viruses results in significant reduction of viral replication. This 23-cGAMP-mediated protection is still observed in flies mutant for the genes Atg7 and AGO2, which encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, it is abrogated in flies mutant for the NF-{kappa}B transcription factor Relish. Analysis of the transcriptome of 23-cGAMP injected flies reveals a complex pattern of response, with early and late induced genes. Our results reveal that dSTING regulates an NF-{kappa}B-dependent antiviral program, which predates the emergence of Interferon Regulatory Factors and interferons in vertebrates.

immunology