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An evolutionarily conserved transcriptional response to viral infection in Caenorhabditis nematodes.

ABSTRACT: Caenorhabditis elegans is a powerful model organism for probing many biological processes including host-pathogen interactions with bacteria and fungi. The recent identification of nematode viruses that naturally infect C. elegans and Caenorhabditis briggsae provides a unique opportunity to define host-virus interactions in these model hosts.We analyzed the transcriptional response of pathogen infected C. elegans and C. briggsae by RNA-seq. We identified a total of 320 differentially expressed genes (DEGs) in C. elegans following Orsay virus infection. The DEGs of known function were enriched for ubiquitin ligase related genes; however, the majority of the genes were of unknown function. Interestingly, many DEGs that responded to Orsay virus infection were similar to those induced by Nematocida parisii infection, which is a natural microsporidia pathogen of C. elegans that like Orsay virus infects intestinal cells. Furthermore, comparison of the Orsay virus DEGs in C. elegans to Santeuil virus DEGs in C. briggsae identified 58 C. elegans genes whose orthologs were likewise differentially expressed in C. briggsae, thereby defining an evolutionarily conserved response to viral infection.The two different species C. elegans and C. briggsae, which diverged ~18 million years ago, share a common set of transcriptionally responsive genes to viral infection. Furthermore, a subset of these genes were also differentially expressed following infection by a eukaryotic pathogen, N. parisii, suggesting that these genes may constitute a broader pan-microbial response to infection.

SUBMITTER: Chen K

PROVIDER: S-EPMC5392922 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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An evolutionarily conserved transcriptional response to viral infection in Caenorhabditis nematodes.

Chen Kevin K Franz Carl J CJ Jiang Hongbing H Jiang Yanfang Y Wang David D

BMC genomics 20170417 1

<h4>Background</h4>Caenorhabditis elegans is a powerful model organism for probing many biological processes including host-pathogen interactions with bacteria and fungi. The recent identification of nematode viruses that naturally infect C. elegans and Caenorhabditis briggsae provides a unique opportunity to define host-virus interactions in these model hosts.<h4>Results</h4>We analyzed the transcriptional response of pathogen infected C. elegans and C. briggsae by RNA-seq. We identified a tota ...[more]

PMID: 28415971

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Project description:BackgroundUnderstanding the molecular mechanisms controlling pluripotency in embryonic stem cells (ESCs) is of central importance towards realizing their potentials in medicine and science. Cross-species examination of transcriptional co-expression allows elucidation of fundamental and species-specific mechanisms regulating ESC self-renewal or differentiation.Methodology/principal findingsWe examined transcriptional co-expression of ESCs from pathways to global networks under the framework of human-mouse comparisons. Using generalized singular value decomposition and comparative partition around medoids algorithms, evolutionarily conserved and divergent transcriptional co-expression regulating pluripotency were identified from ESC-critical pathways including ACTIVIN/NODAL, ATK/PTEN, BMP, CELL CYCLE, JAK/STAT, PI3K, TGFbeta and WNT. A set of transcription factors, including FOX, GATA, MYB, NANOG, OCT, PAX, SOX and STAT, and the FGF response element were identified that represent key regulators underlying the transcriptional co-expression. By transcriptional intervention conducted in silico, dynamic behavior of pathways was examined, which demonstrate how much and in which specific ways each gene or gene combination effects the behavior transition of a pathway in response to ESC differentiation or pluripotency induction. The global co-expression networks of ESCs were dominated by highly connected hub genes such as IGF2, JARID2, LCK, MYCN, NASP, OCT4, ORC1L, PHC1 and RUVBL1, which are possibly critical in determining the fate of ESCs.Conclusions/significanceThrough these studies, evolutionary conservation at genomic, transcriptomic, and network levels is shown to be an effective predictor of molecular factors and mechanisms controlling ESC development. Various hypotheses regarding mechanisms controlling ESC development were generated, which could be further validated by in vitro experiments. Our findings shed light on the systems-level understanding of how ESC differentiation or pluripotency arises from the connectivity or networks of genes, and provide a "road-map" for further experimental investigation.

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An evolutionarily conserved transcriptional response to viral infection in Caenorhabditis nematodes.

Publications

An evolutionarily conserved transcriptional response to viral infection in Caenorhabditis nematodes.

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