The Antiviral RNA Interference Response Provides Resistance to Lethal Arbovirus Infection and Vertical Transmission in Caenorhabditis elegans

Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal Silverman, Craig C. Mello

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)795-806
Number of pages12
JournalCurrent Biology
Volume27
Issue number6
DOIs
StatePublished - Mar 20 2017

Keywords

  • Caenorhabditis elegans
  • RNA interference
  • antiviral immunity
  • arbovirus
  • small RNAs
  • transgenerational inheritance
  • vertical transmission
  • vesicular stomatitis virus
  • virus-host interactions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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