-
[
J Virol,
2012]
Orsay virus and Santeuil virus, the first known viruses capable of naturally infecting the nematodes Caenorhabditis elegans and Caenorhabditis briggsae, respectively, were recently identified by high-throughput sequencing of wild Caenorhabditis strains. By similar analysis of another wild C. briggsae isolate, we have now discovered and sequenced the complete genome of a third novel virus, Le Blanc virus, that is distantly related to Orsay and Santeuil viruses. All three viruses are positive-sense RNA viruses with bipartite genomes that are most closely related to nodaviruses. Identification of a third virus capable of infecting Caenorhabditis nematodes enables comparative analysis of this clade of viruses and strengthens this model for investigating virus-host interactions.
-
[
Virology,
2014]
The discoveries of Orsay, Santeuil and Le Blanc viruses, three viruses infecting either Caenorhabditis elegans or its relative Caenorhabditis briggsae, enable the study of virus-host interactions using natural pathogens of these two well-established model organisms. We characterized the tissue tropism of infection in Caenorhabditis nematodes by these viruses. Using immunofluorescence assays targeting proteins from each of the viruses, and in situ hybridization, we demonstrate viral proteins and RNAs localize to intestinal cells in larval stage Caenorhabditis nematodes. Viral proteins were detected in one to six of the 20 intestinal cells present in Caenorhabditis nematodes. In Orsay virus-infected C. elegans, viral proteins were detected as early as 6h post-infection. The RNA-dependent RNA polymerase and capsid proteins of Orsay virus exhibited different subcellular localization patterns. Collectively, these observations provide the first experimental insights into viral protein expression in any nematode host, and broaden our understanding of viral infection in Caenorhabditis nematodes.
-
[
J Virol,
2019]
Three RNA viruses related to nodaviruses were previously described to naturally infect the nematode <i>Caenorhabditis elegans</i> and its relative <i>Caenorhabditis briggsae.</i> Here we report on a collection of over 50 viral variants from wild-caught <i>Caenorhabditis.</i> We describe the discovery of a new related virus, the Mlnik virus, infecting <i>C. briggsae</i>, which similarly infects intestinal cells. In France, a frequent pattern of co-infection of <i>C. briggsae</i> by the Santeuil virus and Le Blanc virus was observed at the level of an individual nematode and even a single cell. We do not find evidence of reassortment between the RNA1 and RNA2 molecules of Santeuil and Le Blanc viruses. However, by studying patterns of evolution of each virus, reassortments of RNA1 and RNA2 among variants of each virus were identified. We develop assays to test the relative infectivity and competitive ability of the viral variants and detect an interaction between host genotype and Santeuil virus genotype, such that the result depends on the host strain.<b>IMPORTANCE</b> The roundworm <i>Caenorhabditis elegans</i> is a laboratory model organism in biology. We study natural populations of this small animal and its relative <i>C. briggsae</i> and the viruses that infect them. We previously discovered three RNA viruses related to nodaviruses and here describe a fourth one, called the Mlnik virus. These viruses have a genome composed of two RNA molecules. We find that two viruses may infect the same animal and the same cell. The two RNA molecules may be exchanged between variants of a given viral species. We study the diversity of each viral species and devise an assay of their infectivity and competitive ability. Using this assay, we show that the outcome of the competition also depends on the host.
-
Zhou Y, Holt MV, Fan Y, Wang D, Wang T, Guo YR, Zhong W, Tao YJ, Zhang JL, Jin M, Young NL, Jiang H
[
J Virol,
2020]
Fiber proteins are commonly found in eukaryotic and prokaryotic viruses where they play important roles in mediating viral attachment and host cell entry. They typically form trimeric structures and are incorporated into virions via non-covalent interactions. The small RNA virus Orsay, which specifically infects the laboratory model <i>Caenorhabditis elegans</i>, encodes a fibrous protein that can be expressed as a free protein and as a capsid protein- (CP-) fusion protein. Free has previously been demonstrated to facilitate viral exit following intracellular expression; however, the biological significance and prevalence of CP- remained relatively unknown. Here, we demonstrate that Orsay CP- is covalently incorporated into infectious particles, the first example of any attached viral fibers known to date. The crystal structure of (1-101) (<i>i.e.</i> a deletion mutant containing the first 101 amino acid (aa) residues of ) reveals a pentameric, 145-A long fiber with an N-terminal coiled coil followed by multiple -bracelet repeats. Electron micrographs of infectious virions depict particle-associated CP- fibers with dimensions similar to free . proteins from two other nematode viruses Le Blanc and Santeuil, which both specifically infect <i>Caenorhabditis briggsae,</i> were also found to form fibrous molecules. Recombinant Le Blanc was able to block Orsay virus infection in worm culture and vice versa, suggesting these two viruses likely compete for the same cell receptor(s). Thus, we propose that while CP- likely mediates host cell attachment for all three nematode viruses, additional downstream factor(s) ultimately determine the host specificity and range of each virus.<b>IMPORTANCE</b> Viruses often have extended fibers to mediate host cell recognition and entry, serving as promising targets for antiviral drug development. Unlike other known viral fibers, the proteins from the three recently discovered nematode viruses are incorporated into infectious particles as protruding fibers covalently linked to the capsid. Crystal structures of revealed novel pentameric folding repeats, which we term -bracelets, in the intermediate shaft region. Based on sequence analysis, the -bracelet motif of is conserved in all three nematode viruses and could account for 60% of the total length of the fiber. Our study indicated that plays important roles in cell attachment for this group of nematode viruses. In addition, the tightly knitted -bracelet fold, which presumably allows to survive harsh environments in the worm gut, could serve applicable to bioengineering applications given its potentially high stability.
-
[
Annu Rev Genet,
2019]
<i>Caenorhabditis elegans</i> 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 <i>C. elegans</i> (Orsay virus) and its relative <i>Caenorhabditis briggsae</i> (Santeuil virus, Le Blanc virus, and Melnik virus). All are RNA positive-sense viruses related to <i>Nodaviridae</i>; 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. Expected final online publication date for the <i>Annual Review of Genetics</i>, Volume 53 is November 23, 2019. Please see
http://www.annualreviews.org/page/journal/pubdates for revised estimates.
-
[
PLoS Pathog,
2024]
Antagonistic relationships such as host-virus interactions potentially lead to rapid evolution and specificity in interactions. The Orsay virus is so far the only horizontal virus naturally infecting the nematode C. elegans. In contrast, several related RNA viruses infect its congener C. briggsae, including Santeuil (SANTV) and Le Blanc (LEBV) viruses. Here we focus on the host's intraspecific variation in sensitivity to these two intestinal viruses. Many temperate-origin C. briggsae strains, including JU1264 and JU1498, are sensitive to both, while many tropical strains, such as AF16, are resistant to both. Interestingly, some C. briggsae strains exhibit a specific resistance, such as the HK104 strain, specifically resistant to LEBV. The viral sensitivity pattern matches the strains' geographic and genomic relationships. The heavily infected strains mount a seemingly normal small RNA response that is insufficient to suppress viral infection, while the resistant strains show no small RNA response, suggesting an early block in viral entry or replication. We use a genetic approach from the host side to map genomic regions participating in viral resistance polymorphisms. Using Advanced Intercrossed Recombinant Inbred Lines (RILs) between virus-resistant AF16 and SANTV-sensitive HK104, we detect Quantitative Trait Loci (QTLs) on chromosomes IV and III. Building RILs between virus-sensitive JU1498 and LEBV-resistant HK104 followed by bulk segregant analysis, we identify a chromosome II QTL. In both cases, further introgressions of the regions confirmed the QTLs. This diversity provides an avenue for studying virus entry, replication, and exit mechanisms, as well as host-virus specificity and the host response to a specific virus infection.
-
Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO
[
Sci Rep,
2021]
The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).
-
[
Front Pharmacol,
2020]
Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.
-
[
Naturwissenschaften,
2004]
Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.
-
[
J Antibiot (Tokyo),
1990]
Cochlioquinone A, isolated from the fungus Helminthosporium sativum, was found to have nematocidal activity. Cochlioquinone A is a competitive inhibitor of specific [3H]ivermectin binding suggesting that cochlioquinone A and ivermectin interact with the same membrane receptor.