Role of STA-1 and SID-3 upon Orsay virus infection in C. elegans
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE95230 | GEO | 2017/08/11
SECONDARY ACCESSION(S): PRJNA376445
REPOSITORIES: GEO
Similar Datasets
Project description:Across metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes. In the nematode C. elegans, which lacks the interferon system, the major antiviral response so far described is RNA interference but whether additional gene expression responses are employed is not known. Here we show that, despite the absence of both interferon and JAK, the C. elegans STAT homologue STA-1 orchestrates antiviral immunity. Intriguingly, mutants lacking STA-1 show increased resistance to antiviral infection. Using gene expression analysis and chromatin immunoprecipitation we show that, in contrast to the mammalian pathway, STA-1 acts as a transcriptional repressor. Thus STA-1 might act to suppress a constitutive antiviral response in the absence of infection. Using a reverse genetic screen we identify the SID-3 as a kinase upstream of STA-1 in the response to infection. Together, our work identifies a novel STAT regulatory cascade controlling its activity in antiviral resistance, illustrating the complex evolutionary trajectory displayed by innate immune signaling pathways across metazoan organisms.
2017-08-11 | GSE95229 | GEO
Project description:Across metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes. In the nematode C. elegans, which lacks the interferon system, the major antiviral response so far described is RNA interference but whether additional gene expression responses are employed is not known. Here we show that, despite the absence of both interferon and JAK, the C. elegans STAT homologue STA-1 orchestrates antiviral immunity. Intriguingly, mutants lacking STA-1 show increased resistance to antiviral infection. Using gene expression analysis and chromatin immunoprecipitation we show that, in contrast to the mammalian pathway, STA-1 acts as a transcriptional repressor. Thus STA-1 might act to suppress a constitutive antiviral response in the absence of infection. Using a reverse genetic screen we identify the SID-3 as a kinase upstream of STA-1 in the response to infection. Together, our work identifies a novel STAT regulatory cascade controlling its activity in antiviral resistance, illustrating the complex evolutionary trajectory displayed by innate immune signaling pathways across metazoan organisms.
2017-08-11 | GSE95228 | GEO
Project description:Role of STA-1 and SID-3 upon Orsay virus infection in C. elegans
| PRJNA376445 | ENA
Project description:Microbes associated with an organism can significantly modulate its susceptibility to viral infections, but our understanding of the influence of individual microbes remains limited. The nematode Caenorhabditis elegans is a model organism that in nature inhabits environments rich in bacteria. Here, we examine the impact of 71 naturally associated bacteria on C. elegans susceptibility to its only known natural virus, the Orsay virus. Our findings reveal that viral infection of C. elegans is significantly influenced by monobacterial environments. Compared to an Escherichia coli environmental reference, the majority of tested bacteria reduced C. elegans susceptibility to viral infection. This reduction is not caused by virion degradation or poor animal nutrition by the bacteria. The repression of viral infection by the bacterial strains Chryseobacterium JUb44 and Sphingobacterium BIGb0172 does not require the RIG-I homolog DRH-1, which is known to activate antiviral responses such as RNA interference and transcriptional regulation. Our research highlights the necessity of considering natural biotic environments in viral infection studies and opens the way future research on host-microbe-virus interactions.
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Project description:The nematode Caenorhabditis elegans has been a versatile model for understanding the molecular responses to abiotic stress and pathogens. In particular, the response to heat stress and virus infection has been studied in detail. The Orsay virus (OrV) is a natural virus of C. elegans and infection leads to intracellular infection and proteostatic stress, which activates the intracellular pathogen response (IPR). IPR related gene expression is regulated by the genes pals-22 and pals-25, which also control thermotolerance and immunity against other natural pathogens. So far, we have a limited understanding of the molecular responses upon the combined exposure to heat stress and virus infection. We test the hypothesis that the response of C. elegans to OrV infection and heat stress are co-regulated and may affect each other. We conducted a combined heat-stress-virus infection assay and found that after applying heat stress, the susceptibility of C. elegans to OrV was decreased. This difference was found across different wild types of C. elegans. Transcriptome analysis revealed a list of potential candidate genes associated with heat stress and OrV infection. Subsequent mutant screens suggest that pals-22 provides a link between viral response and heat stress, leading to enhanced OrV tolerance of C. elegans after heat stress.
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Project description:Orsay virus (OrV) is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi). However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model.
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Project description:The status of intestinal microbiota is a determinant of host health. However, the alteration of the gut microbiota caused by the innate immune response to virus infection is unclear. Caenorhabditis elegans and its natural virus Orsay provide an excellent model of host-virus interactions. We evaluated the intestinal microbial community complexity of the wild-type N2 and the innate immunity-deficient mutant rde-1 (ne219) strains of C. elegans upon Orsay virus infection. The gut microbiota diversity was decreased in rde-1 (ne219) mutant animals, and a large number of genes were associated with the difference between infected and uninfected rde-1 (ne219) mutant animals. Therefore, this study provides the first evaluation of the alterations caused by Orsay virus on intestinal microbiota in wildtype and innate immunity-deficient animals using C. elegans as the model species. Our findings indicate that virus infection may alters the microbiome in animals with defective immune response.
| S-EPMC5446984 | biostudies-literature
Project description:The recent identification of Orsay virus, the first virus that is capable of naturally infecting Caenorhabditis elegans, provides a unique opportunity to explore host-virus interaction studies in this invaluable model organism. A key feature of this system is the robust genetic tractability of the host, C. elegans, which would ideally be complemented by the ability to genetically manipulate Orsay virus in parallel. To this end, we developed a plasmid-based reverse genetics system for Orsay virus by creating transgenic C. elegans strains harboring Orsay virus cDNAs. Both wild-type and mutant Orsay viruses, including a FLAG epitope-tagged recombinant Orsay virus, were generated by use of the reverse genetics system. This is the first plasmid-based virus reverse genetics system in the metazoan C. elegans. The Orsay virus reverse genetics we established will serve as a fundamental tool in host-virus interaction studies in the model organism C. elegans. Importance: To date, Orsay virus is the first and the only identified virus capable of naturally infecting Caenorhabditis elegans. C. elegans is a simple multicellular model organism that mimics many fundamental features of human biology and has been used to define many biological properties conserved through evolution. Thus, the Orsay virus-C. elegans infection system provides a unique opportunity to study host-virus interactions. In order to take maximal advantage of this system, the ability to genetically engineer mutant forms of Orsay virus would be highly desirable. Most efforts to engineer viruses have been done with cultured cells. Here we describe the creation of mutant viruses directly in the multicellular organism C. elegans without the use of cell culture. We engineered a virus expressing a genetically tagged protein that could be detected in C. elegans. This provides proof of concept for modifying Orsay virus, which will greatly facilitate studies in this experimental system.
| S-EPMC4178717 | biostudies-literature
Project description:Analysis of the transcriptional response to viral infection in C.elegans.
2013-06-01 | GSE41056 | GEO
Project description:Analysis of the transcriptional response to viral infection in C.elegans. Comparison of infected and uninfected animals for three strains: N2 (resistant), JU1580 (sensitive), RDE-1 (sensitive)
2013-06-01 | E-GEOD-41056 | biostudies-arrayexpress