scholarly journals Developing an empirical model for spillover and emergence: Orsay virus host range in Caenorhabditis

2021 ◽  
Author(s):  
Clara L. Shaw ◽  
David A. Kennedy
Keyword(s):  
Rna Virus ◽  
Serial Passage ◽  
Transmitted Infection ◽  
C Elegans ◽  
Experimental Systems ◽  
Positive Sense ◽  
Wild Strains ◽  
Caenorhabditis Species ◽  
Host Phylogeny ◽  
Orsay Virus

A lack of tractable experimental systems in which to test hypotheses about the ecological and evolutionary drivers of disease spillover and emergence has limited our understanding of these processes. Here we introduce a promising system: Caenorhabditis hosts and Orsay virus, a positive-sense single-stranded RNA virus that naturally infects C. elegans. We assayed the susceptibility of species across the Caenorhabditis tree and found 21 of 84 wild strains belonging to 14 of 44 species to be susceptible to Orsay virus. Confirming patterns documented in other systems, we detected effects of host phylogeny on susceptibility. We then tested whether susceptible strains were capable of transmitting Orsay virus by transplanting exposed hosts and determining whether they transmitted infection to conspecifics during serial passage. We found no evidence of transmission in 10 strains (virus undetectable after passaging), evidence of low-level transmission in 5 strains (virus lost between passage 1 and 5), and evidence of sustained transmission in 6 strains (including all 3 experimental C. elegans strains). Transmission was associated with host phylogeny and with viral amplification in exposed populations. Variation in Orsay virus susceptibility and transmission among Caenorhabditis species suggests that the system could be powerful for studying spillover and emergence.

scholarly journals Deep sampling of Hawaiian Caenorhabditis elegans reveals high genetic diversity and admixture with global populations

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tim A Crombie ◽  
Stefan Zdraljevic ◽  
Daniel E Cook ◽  
Robyn E Tanny ◽  
Shannon C Brady ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Caenorhabditis Elegans ◽  
Nematode Species ◽  
Specific Substrate ◽  
High Genetic Diversity ◽  
C Elegans ◽  
Worldwide Population ◽  
Shared Ancestry ◽  
Wild Strains ◽  
Caenorhabditis Species

Hawaiian isolates of the nematode species Caenorhabditis elegans have long been known to harbor genetic diversity greater than the rest of the worldwide population, but this observation was supported by only a small number of wild strains. To better characterize the niche and genetic diversity of Hawaiian C. elegans and other Caenorhabditis species, we sampled different substrates and niches across the Hawaiian islands. We identified hundreds of new Caenorhabditis strains from known species and a new species, Caenorhabditis oiwi. Hawaiian C. elegans are found in cooler climates at high elevations but are not associated with any specific substrate, as compared to other Caenorhabditis species. Surprisingly, admixture analysis revealed evidence of shared ancestry between some Hawaiian and non-Hawaiian C. elegans strains. We suggest that the deep diversity we observed in Hawaii might represent patterns of ancestral genetic diversity in the C. elegans species before human influence.

scholarly journals The predicted bZIP transcription factor ZIP-1 promotes resistance to intracellular infection in Caenorhabditis elegans

2021 ◽  
Author(s):  
Vladimir Lazetic ◽  
Fengting Wu ◽  
Lianne B Cohen ◽  
Kirthi C Reddy ◽  
Ya-Ting Chang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Rna Virus ◽  
Bzip Transcription Factor ◽  
Intestinal Cells ◽  
Intracellular Pathogen ◽  
Regulatory Pathways ◽  
Intracellular Infection ◽  
C Elegans ◽  
Orsay Virus

Defense against intracellular infection has been extensively studied in vertebrate hosts, but less is known about invertebrate hosts. For example, almost nothing is known about the transcription factors that induce defense against intracellular infection in the model nematode Caenorhabditis elegans. Two types of intracellular pathogens that naturally infect C. elegans are the Orsay virus, which is a positive-sense RNA virus, and microsporidia, which are fungal pathogens. Surprisingly, these molecularly distinct pathogens induce a common host transcriptional response called the Intracellular Pathogen Response (IPR). Here we describe zip-1 as an IPR regulator that functions downstream of all known IPR activating and regulatory pathways. zip-1 encodes a putative bZIP transcription factor of previously unknown function, and we show how zip-1 controls induction of a subset of genes upon IPR activation. ZIP-1 protein is expressed in the nuclei of intestinal cells, and is required in the intestine to upregulate IPR gene expression. Importantly, zip-1 promotes resistance to infection by the Orsay virus and by microsporidia in intestinal cells. Altogether, our results indicate that zip-1 represents a central hub for all triggers of the IPR, and that this transcription factor plays a protective role against intracellular pathogen infection in C. elegans.

scholarly journals Orsay δ Protein Is Required for Nonlytic Viral Egress

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Wang Yuan ◽  
Ying Zhou ◽  
Yanlin Fan ◽  
Yizhi J. Tao ◽  
Weiwei Zhong
Keyword(s):  
Rna Virus ◽  
Nonstructural Protein ◽  
Mutant Virus ◽  
Host Cells ◽  
Apical Surface ◽  
Content Type ◽  
C Elegans ◽  
Apical Side ◽  
Orsay Virus

ABSTRACTNonenveloped gastrointestinal viruses, such as human rotavirus, can exit infected cells from the apical surface without cell lysis. The mechanism of such nonlytic exit is poorly understood. The nonenveloped Orsay virus is an RNA virus infecting the intestine cells of the nematodeCaenorhabditis elegans. Dye staining results suggested that Orsay virus exits from the intestine of infected worms in a nonlytic manner. Therefore, the Orsay virus-C. eleganssystem provides an excellentin vivomodel to study viral exit. The Orsay virus genome encodes three proteins: RNA-dependent RNA polymerase, capsid protein (CP), and a nonstructural protein, δ. δ can also be expressed as a structural CP-δ fusion. We generated an ATG-to-CTG mutant virus that had a normal CP-δ fusion but could not produce free δ due to the lack of the start codon. This mutant virus showed a viral exit defect without obvious phenotypes in other steps of viral infection, suggesting that δ is involved in viral exit. Ectopically expressed free δ localized near the apical membrane of intestine cells inC. elegansand colocalized with ACT-5, an intestine-specific actin that is a component of the terminal web. Orsay virus infection rearranged ACT-5 apical localization. Reduction of the ACT-5 level via RNA interference (RNAi) significantly exacerbated the viral exit defect of the δ mutant virus, suggesting that δ and ACT-5 functionally interact to promote Orsay virus exit. Together, these data support a model in which the viral δ protein interacts with the actin network at the apical side of host intestine cells to mediate the polarized, nonlytic egress of Orsay virus.IMPORTANCEAn important step of the viral life cycle is how viruses exit from host cells to spread to other cells. Certain nonenveloped viruses can exit cultured cells in nonlytic ways; however, such nonlytic exit has not been demonstratedin vivo. In addition, it is not clear how such nonlytic exit is achieved mechanisticallyin vivo. Orsay virus is a nonenveloped RNA virus that infects the intestine cells of the nematodeC. elegans. It is currently the only virus known to naturally infectC. elegans. Using thisin vivomodel, we show that the δ protein encoded by Orsay virus facilitates the nonlytic exit of the virus, possibly by interacting with host actin on the apical side of worm intestine cells.

Natural Viruses of Caenorhabditis Nematodes

2019 ◽  
Vol 53 (1) ◽  
pp. 313-326 ◽  
Author(s):  
Marie-Anne Félix ◽  
David Wang
Keyword(s):  
Model Organism ◽  
Laboratory Model ◽  
Intestinal Cells ◽  
Caenorhabditis Briggsae ◽  
C Elegans ◽  
The Past ◽  
Antiviral Genes ◽  
Evolutionarily Conserved ◽  
Positive Sense ◽  
Orsay Virus

Caenorhabditis elegans has long been a laboratory model organism with no known natural pathogens. In the past ten years, however, natural viruses have been isolated from wild-caught C. elegans (Orsay virus) and its relative Caenorhabditis briggsae (Santeuil virus, Le Blanc virus, and Melnik virus). All are RNA positive-sense viruses related to Nodaviridae; they infect intestinal cells and are horizontally transmitted. The Orsay virus capsid structure has been determined and the virus can be reconstituted by transgenesis of the host. Recent use of the Orsay virus has enabled researchers to identify evolutionarily conserved proviral and antiviral genes that function in nematodes and mammals. These pathways include endocytosis through SID-3 and WASP; a uridylyltransferase that destabilizes viral RNAs by uridylation of their 3′ end; ubiquitin protein modifications and turnover; and the RNA interference pathway, which recognizes and degrades viral RNA.

scholarly journals Antiviral RNA Interference against Orsay Virus Is neither Systemic nor Transgenerational in Caenorhabditis elegans

2015 ◽  
Vol 89 (23) ◽  
pp. 12035-12046 ◽  
Author(s):  
Alyson Ashe ◽  
Peter Sarkies ◽  
Jérémie Le Pen ◽  
Mélanie Tanguy ◽  
Eric A. Miska
Keyword(s):  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Viral Infection ◽  
Rna Virus ◽  
Rnai Pathway ◽  
Content Type ◽  
C Elegans ◽  
Systemic Rnai ◽  
Endogenous Role ◽  
Orsay Virus

ABSTRACTAntiviral RNA-mediated silencing (RNA interference [RNAi]) acts as a powerful innate immunity defense in plants, invertebrates, and mammals. InCaenorhabditis elegans, RNAi is systemic; i.e., RNAi silencing signals can move between cells and tissues. Furthermore, RNAi effects can be inherited transgenerationally and may last for many generations. Neither the biological relevance of systemic RNAi nor transgenerational RNAi is currently understood. Here we examined the role of both pathways in the protection ofC. elegansfrom viral infection. We studied the Orsay virus, a positive-strand RNA virus related toNodaviridaeand the first and only virus known to infectC. elegans. Immunity to Orsay virus infection requires the RNAi pathway. Surprisingly, we found that genes required for systemic or transgenerational RNAi did not have a role in antiviral defense. Furthermore, we found that Orsay virus infection did not elicit a systemic RNAi response even when a target for RNAi was provided by using transgenes. Finally, we show that viral siRNAs, the effectors of RNAi, are not inherited to a level that provides any significant resistance to viral infection in the next generation. We conclude that systemic or transgenerational RNAi does not play a role in the defense against natural Orsay virus infection. Furthermore, our data suggest that there is a qualitative difference between experimental RNAi and antiviral RNAi. Our data are consistent with a model of systemic and transgenerational RNAi that requires a nuclear or germ line component that is lacking in almost all RNA virus infections.IMPORTANCESince its discovery inCaenorhabditis elegans, RNAi has proven a valuable scientific tool in many organisms. InC. elegans, exogenous RNAi spreads throughout the organism and can be passed between generations; however, there has been controversy as to the endogenous role(s) that the RNAi pathway plays. One endogenous role for which spreading both within the infected organism and between generations would be advantageous is a role in viral defense. In plants, antiviral RNAi is systemic and the spread of RNAi between cells provides protection against subsequent viral infection. Here we investigated this by using the only naturally occurring virus known to infectC. elegans, Orsay virus, and surprisingly found that, in contrast to the exogenous RNAi pathway, the antiviral RNAi response targeted against this virus does not spread systemically throughout the organism and cannot be passed between generations. These results suggest that there are differences between the two pathways that remain to be discovered.

scholarly journals Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1161
Author(s):  
Yuqing Huang ◽  
Mark G. Sterken ◽  
Koen van Zwet ◽  
Lisa van Sluijs ◽  
Gorben P. Pijlman ◽  
...  
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Intracellular Pathogen ◽  
Potential Candidate ◽  
Molecular Responses ◽  
C Elegans ◽  
Pathogen Response ◽  
Orsay Virus ◽  
Natural Virus

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.

scholarly journals Origins and Evolution of the Global RNA Virome

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Yuri I. Wolf ◽  
Darius Kazlauskas ◽  
Jaime Iranzo ◽  
Adriana Lucía-Sanz ◽  
Jens H. Kuhn ◽  
...  
Keyword(s):  
Plant Pathogens ◽  
Rna Viruses ◽  
Rna Virus ◽  
Phylogenomic Analysis ◽  
Rna Helicases ◽  
Sequence Alignments ◽  
Recent Advances ◽  
Wide Range ◽  
Positive Sense ◽  
Dsrna Viruses

ABSTRACTViruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas −RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.IMPORTANCEThe majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than was attainable previously. This reconstruction reveals the relationships between different Baltimore classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.

scholarly journals An Evolutionarily Conserved Pathway Essential for Orsay Virus Infection of Caenorhabditis elegans

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Hongbing Jiang ◽  
Kevin Chen ◽  
Luis E. Sandoval ◽  
Christian Leung ◽  
David Wang
Keyword(s):  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Tyrosine Kinase ◽  
Model Organism ◽  
Wiskott Aldrich Syndrome ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Conserved Genes ◽  
Orsay Virus ◽  
Syndrome Protein

ABSTRACT Many fundamental biological discoveries have been made in Caenorhabditis elegans. The discovery of Orsay virus has enabled studies of host-virus interactions in this model organism. To identify host factors critical for Orsay virus infection, we designed a forward genetic screen that utilizes a virally induced green fluorescent protein (GFP) reporter. Following chemical mutagenesis, two Viro (virus induced reporter off) mutants that failed to express GFP were mapped to sid-3, a nonreceptor tyrosine kinase, and B0280.13 (renamed viro-2), an ortholog of human Wiskott-Aldrich syndrome protein (WASP). Both mutants yielded Orsay virus RNA levels comparable to that of the residual input virus, suggesting that they are not permissive for Orsay virus replication. In addition, we demonstrated that both genes affect an early prereplication stage of Orsay virus infection. Furthermore, it is known that the human ortholog of SID-3, activated CDC42-associated kinase (ACK1/TNK2), is capable of phosphorylating human WASP, suggesting that VIRO-2 may be a substrate for SID-3 in C. elegans. A targeted RNA interference (RNAi) knockdown screen further identified the C. elegans gene nck-1, which has a human ortholog that interacts with TNK2 and WASP, as required for Orsay virus infection. Thus, genetic screening in C. elegans identified critical roles in virus infection for evolutionarily conserved genes in a known human pathway. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection.

Novel positive-sense single-stranded RNA virus related to alphavirus-like viruses from Fusarium graminearum

2019 ◽  
Vol 165 (2) ◽  
pp. 487-490
Author(s):  
Xing Zhang ◽  
Haotian Zhang ◽  
Dongfang Ma ◽  
Huaigu Chen ◽  
Wei Li
Keyword(s):  
Fusarium Graminearum ◽  
Rna Virus ◽  
Positive Sense

scholarly journals Novel RNA Virus Genome Discovered in Ghost Ants (Tapinoma melanocephalum) from Hawaii

2017 ◽  
Vol 5 (30) ◽  
Author(s):  
Laura E. Brettell ◽  
Gideon J. Mordecai ◽  
Purnima Pachori ◽  
Stephen J. Martin
Keyword(s):  
Amino Acids ◽  
Genome Sequence ◽  
Rna Virus ◽  
Virus Genome ◽  
Full Genome Sequence ◽  
Full Genome ◽  
Tapinoma Melanocephalum ◽  
Positive Sense

ABSTRACT Here, we report the full-genome sequence of Milolii virus, a novel single-stranded (positive-sense) RNA virus discovered from Tapinoma melanocephalum ants in Hawaii. The genome is 10,475 nucleotides long, encoding a polyprotein of 3,304 amino acids.

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