TY - JOUR
T1 - The Antiviral RNA Interference Response Provides Resistance to Lethal Arbovirus Infection and Vertical Transmission in Caenorhabditis elegans
AU - Gammon, Don B.
AU - Ishidate, Takao
AU - Li, Lichao
AU - Gu, Weifeng
AU - Silverman, Neal
AU - Mello, Craig C.
N1 - Funding Information:
We thank Dr. Rita Sharma and Ms. Tauny Tambolleo for excellent technical assistance. D.B.G. was supported by fellowships from the Natural Sciences and Engineering Research Council of Canada and Alberta Innovates Health Solutions. C.C.M. was funded by the NIH (grant 5R37GM058800) and is a Howard Hughes Medical Institute Investigator. N.S. was funded by the NIH (grant AI060025).
Publisher Copyright:
© 2017 The Authors
PY - 2017/3/20
Y1 - 2017/3/20
N2 - 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.
AB - 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.
KW - Caenorhabditis elegans
KW - RNA interference
KW - antiviral immunity
KW - arbovirus
KW - small RNAs
KW - transgenerational inheritance
KW - vertical transmission
KW - vesicular stomatitis virus
KW - virus-host interactions
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U2 - 10.1016/j.cub.2017.02.004
DO - 10.1016/j.cub.2017.02.004
M3 - Article
C2 - 28262484
AN - SCOPUS:85014083730
SN - 0960-9822
VL - 27
SP - 795
EP - 806
JO - Current Biology
JF - Current Biology
IS - 6
ER -