Wang, David, Jiang, Hongbing, Wu, Guang, Franz, Carl, Renshaw, Hilary, Chen, Kevin
[
International Worm Meeting,
2015]
Model organisms have played a critical role in our understanding of innate immunity. The recent discovery of Orsay virus, the 1st virus capable of infecting C. elegans, and the discoveries of Santeuil and Le Blanc viruses which infect C. briggsae, provide a unique opportunity to define virus host interactions in these model hosts. In order to identify candidate antiviral genes, we have performed a time course transcriptional profiling with RNA-seq. In C. elegans, we identified 151 genes that were differentially expressed upon Orsay virus infection. In this set, only 36 have annotation; 22 genes contain domains involved in ubiquitin-mediated proteolysis. By further defining the transcriptional response of the orthologous genes in C. briggsae to Santeuil and Le Blanc virus infection, we identified 39 conserved genes induced in both hosts by the three viruses. Strikingly, 17 of the 39 conserved response genes are paralogs of a single gene family that is exemplified by C17H1.3. This gene family has a human ortholog, but no known function has been associated to these orthologous genes. The conserved induction of these genes in response to infection by multiple viruses strongly suggests they may play a role in antiviral defense. Efforts to define such function by targeted gene deletion and overexpression are underway. .
Franz, Carl J., Frezal, Lise, Jiang, Yanfang, Wang, David, Felix, Marie-Anne, Renshaw, Hilary
[
International Worm Meeting,
2013]
Orsay, Santeuil and Le Blanc viruses were recently discovered, enabling for the first time the study of virus-host interactions using a natural pathogen in the well-established model organism Caenorhabditis elegans and its relative Caenorhabditis briggsae. All three viruses share less than 50% amino acid identity and are most closely related to nodaviruses, which are positive sense RNA viruses with bipartite genomes. Comparison of their complete genomes demonstrated unique coding and noncoding features absent in known nodaviruses. Le Blanc virus, similar to Santeuil virus, was capable of infecting wild C. briggsae isolates but not the AF16 C. briggsae laboratory reference strain nor any tested C. elegans strains. We characterized the tissue tropism of infection in Caenorhabditis nematodes by all three viruses. Using immunofluorescence assays targeting viral proteins, as well as in situ hybridization, we demonstrated that viral proteins and RNAs localized primarily to intestinal cells in larval stage Caenorhabditis nematodes. The viral proteins could be detected in one to six of the 20 intestinal cells present in Caenorhabditis nematodes. In Orsay virus-infected C. elegans, viral proteins could be detected as early as six hours post infection. Furthermore, the RNA-dependent RNA polymerase and capsid proteins of Orsay virus exhibited different subcellular localization patterns from each other. Collectively, these observations broaden our understanding of viral infection in Caenorhabditis nematodes.