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      Variation in Antiviral Protection Mediated by Different Wolbachia Strains in Drosophila simulans

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Drosophila C virus (DCV) is a natural pathogen of Drosophila and a useful model for studying antiviral defences. The Drosophila host is also commonly infected with the widespread endosymbiotic bacteria Wolbachia pipientis. When DCV coinfects Wolbachia-infected D. melanogaster, virus particles accumulate more slowly and virus induced mortality is substantially delayed. Considering that Wolbachia is estimated to infect up to two-thirds of all insect species, the observed protective effects of Wolbachia may extend to a range of both beneficial and pest insects, including insects that vector important viral diseases of humans, animals and plants. Currently, Wolbachia-mediated antiviral protection has only been described from a limited number of very closely related strains that infect D. melanogaster. We used D. simulans and its naturally occurring Wolbachia infections to test the generality of the Wolbachia-mediated antiviral protection. We generated paired D. simulans lines either uninfected or infected with five different Wolbachia strains. Each paired fly line was challenged with DCV and Flock House virus. Significant antiviral protection was seen for some but not all of the Wolbachia strain-fly line combinations tested. In some cases, protection from virus-induced mortality was associated with a delay in virus accumulation, but some Wolbachia-infected flies were tolerant to high titres of DCV. The Wolbachia strains that did protect occurred at comparatively high density within the flies and were most closely related to the D. melanogaster Wolbachia strain wMel. These results indicate that Wolbachia-mediated antiviral protection is not ubiquitous, a finding that is important for understanding the distribution of Wolbachia and virus in natural insect populations.

          Author Summary

          Many human, animal and plant viruses are transmitted between hosts by insect vectors. Understanding the processes that control virus infection in insects may facilitate strategies that aim to control the spread of important viral pathogens. Infection of the model insect Drosophila with the endosymbiotic bacteria Wolbachia can significantly affect the outcome of infection with pathogenic viruses. Wolbachia is widespread in insects, so here we tested the generality of antiviral protection across diverse strains of the bacteria. We show that some, but not all, strains of Wolbachia protect flies from pathogenic viruses. These results have implications for proposed strategies utilising Wolbachia to control the spread of insect-transmitted viral diseases, such as dengue.

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          Most cited references29

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          RNA interference directs innate immunity against viruses in adult Drosophila.

          Innate immunity against bacterial and fungal pathogens is mediated by Toll and immune deficiency (Imd) pathways, but little is known about the antiviral response in Drosophila. Here, we demonstrate that an RNA interference pathway protects adult flies from infection by two evolutionarily diverse viruses. Our work also describes a molecular framework for the viral immunity, in which viral double-stranded RNA produced during infection acts as the pathogen trigger whereas Drosophila Dicer-2 and Argonaute-2 act as host sensor and effector, respectively. These findings establish a Drosophila model for studying the innate immunity against viruses in animals.
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            The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster.

            Most organisms have evolved defense mechanisms to protect themselves from viruses and other pathogens. Arthropods lack the protein-based adaptive immune response found in vertebrates. Here we show that the central catalytic component of the RNA-induced silencing complex (RISC), the nuclease Argonaute 2 (Ago-2), is essential for antiviral defense in adult Drosophila melanogaster. Ago-2-defective flies are hypersensitive to infection with a major fruit fly pathogen, Drosophila C virus (DCV), and with Cricket Paralysis virus (CrPV). Increased mortality in ago-2 mutant flies was associated with a dramatic increase in viral RNA accumulation and virus titers. The physiological significance of this antiviral mechanism is underscored by our finding that DCV encodes a potent suppressor of RNA interference (RNAi). This suppressor binds long double-stranded RNA (dsRNA) and inhibits Dicer-2-mediated processing of dsRNA into short interfering RNA (siRNA), but does not bind short siRNAs or disrupt the microRNA (miRNA) pathway. Based on these results we propose that RNAi is a major antiviral immune defense mechanism in Drosophila.
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              The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila.

              The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-kappaB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Pathog
                plos
                plospath
                PLoS Pathogens
                Public Library of Science (San Francisco, USA )
                1553-7366
                1553-7374
                November 2009
                November 2009
                13 November 2009
                : 5
                : 11
                : e1000656
                Affiliations
                [1]School of Biological Sciences, The University of Queensland, St Lucia, Queensland, Australia
                Stanford University, United States of America
                Author notes

                Conceived and designed the experiments: SEO SLO KNJ. Performed the experiments: SEO YSL KNJ. Analyzed the data: SEO YSL KNJ. Wrote the paper: SEO SLO KNJ.

                Article
                09-PLPA-RA-0983R2
                10.1371/journal.ppat.1000656
                2768908
                19911047
                a748e684-d90a-44a8-b4a2-025d0f5fcc21
                Osborne et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 17 June 2009
                : 13 October 2009
                Page count
                Pages: 9
                Categories
                Research Article
                Infectious Diseases/Epidemiology and Control of Infectious Diseases
                Infectious Diseases/Viral Infections
                Microbiology/Immunity to Infections
                Microbiology/Microbial Evolution and Genomics
                Virology/Host Antiviral Responses

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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