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PLoS Pathog DOI:10.1371/journal.ppat.1004200

Ubiquitin-mediated response to microsporidia and virus infection in C. elegans.

Publication TypeJournal Article
Year of Publication2014
AuthorsBakowski, MA, Desjardins, CA, Smelkinson, MG, Dunbar, TL, Dunbar, TA, Lopez-Moyado, IF, Rifkin, SA, Cuomo, CA, Troemel, ER
JournalPLoS Pathog
Volume10
Issue6
Pagese1004200
Date Published2014 Jun
ISSN1553-7374
KeywordsAnimals, Autophagy, Base Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cullin Proteins, Host-Pathogen Interactions, Microsporidia, RNA Interference, RNA, Small Interfering, Sequence Analysis, RNA, SKP Cullin F-Box Protein Ligases, Transcription, Genetic, Ubiquitin, Ubiquitination
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.

URLhttp://dx.plos.org/10.1371/journal.ppat.1004200
DOI10.1371/journal.ppat.1004200
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24945527?dopt=Abstract

Alternate JournalPLoS Pathog.
PubMed ID24945527
PubMed Central IDPMC4063957
Grant ListHHSN272200900018C / AI / NIAID NIH HHS / United States
P40 OD010440 / OD / NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States
R01 AI087528 / AI / NIAID NIH HHS / United States