RNA Therapeutics Institute; Department of Medicine, Division of Infectious Diseases and Immunology
Immunity | Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy | Microbiology
The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C. elegans. Furthermore, we find nematodes deficient for components of the antiviral RNAi pathway, such as Dicer-related helicase 1 (DRH-1), to display hypersusceptibility to VSV infection as evidenced by elevated infection rates, virus replication in multiple tissue types, and earlier mortality. Strikingly, infection of oocytes and embryos could also be observed in drh-1 mutants. Our results suggest that the antiviral RNAi response not only inhibits vertical VSV transmission but also promotes transgenerational inheritance of antiviral immunity. Our study introduces a new, in vivo virus-host model system for exploring arbovirus pathogenesis and provides the first evidence for vertical pathogen transmission in C. elegans.
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Copyright 2017 The Authors. Published by Elsevier Ltd. Citation: Curr Biol. 2017 Mar 20;27(6):795-806. doi: 10.1016/j.cub.2017.02.004. Epub 2017 Mar 2. Link to article on publisher's site
Caenorhabditis elegans, RNA interference, antiviral immunity, arbovirus, small RNAs, transgenerational inheritance, vertical transmission, vesicular stomatitis virus, virus-host interactions
Gammon, Don B.; Ishidate, Takao; Li, Lichao; Gu, Weifeng; Silverman, Neal S.; and Mello, Craig C., "The Antiviral RNA Interference Response Provides Resistance to Lethal Arbovirus Infection and Vertical Transmission in Caenorhabditis elegans" (2017). University of Massachusetts Medical School Faculty Publications. 1292.
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