Natural and Experimental Infection of Caenorhabditis Nematodes by Novel Viruses Related to Nodaviruses

Abstract

Novel viruses have been discovered in wild Caenorahbditis nematode isolates and can now be used to explore host antiviral pathways, nematode ecology, and host-pathogen co-evolution.

Abstract

An ideal model system to study antiviral immunity and host-pathogen co-evolution would combine a genetically tractable small animal with a virus capable of naturally infecting the host organism. The use of C. elegans as a model to define host-viral interactions has been limited by the lack of viruses known to infect nematodes. From wild isolates of C. elegans and C. briggsae with unusual morphological phenotypes in intestinal cells, we identified two novel RNA viruses distantly related to known nodaviruses, one infecting specifically C. elegans (Orsay virus), the other C. briggsae (Santeuil virus). Bleaching of embryos cured infected cultures demonstrating that the viruses are neither stably integrated in the host genome nor transmitted vertically. 0.2 µm filtrates of the infected cultures could infect cured animals. Infected animals continuously maintained viral infection for 6 mo (∼50 generations), demonstrating that natural cycles of horizontal virus transmission were faithfully recapitulated in laboratory culture. In addition to infecting the natural C. elegans isolate, Orsay virus readily infected laboratory C. elegans mutants defective in RNAi and yielded higher levels of viral RNA and infection symptoms as compared to infection of the corresponding wild-type N2 strain. These results demonstrated a clear role for RNAi in the defense against this virus. Furthermore, different wild C. elegans isolates displayed differential susceptibility to infection by Orsay virus, thereby affording genetic approaches to defining antiviral loci. This discovery establishes a bona fide viral infection system to explore the natural ecology of nematodes, host-pathogen co-evolution, the evolution of small RNA responses, and innate antiviral mechanisms.

Author Summary

The nematode C. elegans is a robust model organism that is broadly used in biology. It also has great potential for the study of host-microbe interactions, as it is possible to systematically knockout almost every gene in high-throughput fashion to examine the potential role of each gene in infection. While C. elegans has been successfully applied to the study of bacterial infections, only limited studies of antiviral responses have been possible since no virus capable of infecting any Caenorhabditis nematode in laboratory culture has previously been described. Here we report the discovery of natural viruses infecting wild isolates of C. elegans and its relative C. briggsae. These novel viruses are most closely related to the ssRNA nodaviruses, but have larger genomes than other described nodaviruses and clearly represent a new taxon of virus. We were able to use these viruses to infect a variety of laboratory nematode strains. We show that mutant worms defective in the RNA interference pathway, an antiviral system known to operate in a number of organisms, accumulate more viral RNA than wild type strains. The discovery of these viruses will enable further studies of host-virus interactions in C. elegans and the identification of other host mechanisms that counter viral infection.

Contributors

: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS Biol

Journal ID (publisher-id): plos

Journal ID (pmc): plosbiol

Title: PLoS Biology

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Print): 1544-9173

ISSN (Electronic): 1545-7885

Publication date Collection: January 2011

Publication date (Print): January 2011

Publication date (Electronic): 25 January 2011

Volume: 9

Issue: 1

Affiliations

[1 ]Institut Jacques Monod, CNRS-University of Paris-Diderot, Paris, France

[2 ]Gurdon Institute, University of Cambridge, Cambridge, United Kingdom

[3 ]Departments of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America

Oxford University, United Kingdom

Author notes

* E-mail: felix@ 123456ijm.univ-paris-diderot (MAF); eam29@ 123456cam.ac.uk (EAM); davewang@ 123456wustl.edu (DW)

The author(s) have made the following declarations about their contributions: Conceived and designed the experiments: MAF EAM DW. Performed the experiments: MAF AA JP GW IN TB YJ CJF MS. Analyzed the data: MAF AA JP GW IN TB GZ CJF LDG MS EAM DW. Wrote the paper: MAF AA EAM DW.

Article

Publisher ID: 10-PLBI-RA-8820R2

DOI: 10.1371/journal.pbio.1000586

PMC ID: 3026760

PubMed ID: 21283608

Copyright statement: Félix 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.

Related

Related article ( companion): Nematodes Go Viral

Page count

Pages: 14

Categories

Subject: Research Article

Subject: Ecology/Environmental Microbiology

Subject: Immunology/Innate Immunity

Subject: Virology

Subject: Virology/Animal Models of Infection