title: The Antiviral RNA Interference Response Provides Resistance to Lethal Arbovirus Infection and Vertical Transmission in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: don.gammon@utsouthwestern.edu.
authors.forename: Don B
authors.initials: DB
authors.lastname: Gammon
authors.affiliation: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Takao
authors.initials: T
authors.lastname: Ishidate
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, CA 92521, USA.
authors.forename: Lichao
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, CA 92521, USA.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Silverman
authors.affiliation: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: craig.mello@umassmed.edu.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Mello
mesh_terms: D000818:Animals; D001102:Arbovirus Infections / Q000635:transmission* / Q000821:virology; D017173:Caenorhabditis elegans; D018445:Infectious Disease Transmission, Vertical; D008845:Microinjections; D034622:RNA Interference; D018353:Rhabdoviridae Infections / Q000635:transmission* / Q000821:virology; D018116:Vesiculovirus / Q000502:physiology*
keywords: Caenorhabditis elegans; RNA interference; antiviral immunity; arbovirus; small RNAs; transgenerational inheritance; vertical transmission; vesicular stomatitis virus; virus-host interactions