title: Ubiquitin-mediated response to microsporidia and virus infection in C. elegans.
abstract: Microsporidia comprise a phylum of over 1400 species of obligate intracellular pathogens that can infect almost all animals, but little is known about the host response to these parasites. Here we use the whole-animal host C. elegans to show an in vivo role for ubiquitin-mediated response to the microsporidian species Nematocida parisii, as well to the Orsay virus, another natural intracellular pathogen of C. elegans. We analyze gene expression of C. elegans in response to N. parisii, and find that it is similar to response to viral infection. Notably, we find an upregulation of SCF ubiquitin ligase components, such as the cullin ortholog cul-6, which we show is important for ubiquitin targeting of N. parisii cells in the intestine. We show that ubiquitylation components, the proteasome, and the autophagy pathway are all important for defense against N. parisii infection. We also find that SCF ligase components like cul-6 promote defense against viral infection, where they have a more robust role than against N. parisii infection. This difference may be due to suppression of the host ubiquitylation system by N. parisii: when N. parisii is crippled by anti-microsporidia drugs, the host can more effectively target pathogen cells for ubiquitylation. Intriguingly, inhibition of the ubiquitin-proteasome system (UPS) increases expression of infection-upregulated SCF ligase components, indicating that a trigger for transcriptional response to intracellular infection by N. parisii and virus may be perturbation of the UPS. Altogether, our results demonstrate an in vivo role for ubiquitin-mediated defense against microsporidian and viral infections in C. elegans.
authors.affiliation: Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Malina A
authors.initials: MA
authors.lastname: Bakowski
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Desjardins
authors.affiliation: Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Margery G
authors.initials: MG
authors.lastname: Smelkinson
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Dunbar
authors.affiliation: Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Dunbar
authors.affiliation: Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Isaac F
authors.initials: IF
authors.lastname: Lopez-Moyado
authors.affiliation: Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, California, United States of America; Division of Biological Sciences, Section of Ecology, Behavior, and Evolution University of California San Diego, La Jolla, California, United States of America.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rifkin
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Cuomo
authors.affiliation: Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Troemel
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000276:immunology / Q000469:parasitology* / Q000821:virology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D044842:Cullin Proteins / Q000096:biosynthesis / Q000276:immunology*; D054884:Host-Pathogen Interactions; D016814:Microsporidia / Q000276:immunology / Q000472:pathogenicity*; D034622:RNA Interference; D034741:RNA, Small Interfering; D044843:SKP Cullin F-Box Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics*
chemical_list: C000600610:CUL-6 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D044842:Cullin Proteins; D034741:RNA, Small Interfering; D025801:Ubiquitin; D044843:SKP Cullin F-Box Protein Ligases