RNAi pathways in the recognition of foreign RNA: antiviral responses and host–parasite interactions in nematodes

2013 ◽  
Vol 41 (4) ◽  
pp. 876-880 ◽  
Author(s):  
Peter Sarkies ◽  
Eric A. Miska

The nematode Caenorhabditis elegans was the first animal for which RNAi (RNA interference) in response to exogenous triggers was shown experimentally and subsequently the molecular components of the RNAi pathway have been characterized in some detail. However, the function of RNAi in the life cycle of nematodes in the wild is still unclear. In the present article, we argue that RNAi could be used in nematodes as a mechanism to sense and respond to foreign RNA that the animal might be exposed to either through viral infection or through ingestion of food sources. This could be of potential importance to the life cycle of parasitic nematodes as they ingest RNA from different hosts at different points during their life cycle. We postulate that RNA ingested from the host could be used by the parasite to regulate its own genes, through the amplification mechanism intrinsic to the nematode RNAi pathway.

Genetics ◽  
2020 ◽  
Vol 216 (4) ◽  
pp. 837-878
Author(s):  
L. Ryan Baugh ◽  
Patrick J. Hu

Caenorhabditis elegans survives on ephemeral food sources in the wild, and the species has a variety of adaptive responses to starvation. These features of its life history make the worm a powerful model for studying developmental, behavioral, and metabolic starvation responses. Starvation resistance is fundamental to life in the wild, and it is relevant to aging and common diseases such as cancer and diabetes. Worms respond to acute starvation at different times in the life cycle by arresting development and altering gene expression and metabolism. They also anticipate starvation during early larval development, engaging an alternative developmental program resulting in dauer diapause. By arresting development, these responses postpone growth and reproduction until feeding resumes. A common set of signaling pathways mediates systemic regulation of development in each context but with important distinctions. Several aspects of behavior, including feeding, foraging, taxis, egg laying, sleep, and associative learning, are also affected by starvation. A variety of conserved signaling, gene regulatory, and metabolic mechanisms support adaptation to starvation. Early life starvation can have persistent effects on adults and their descendants. With its short generation time, C. elegans is an ideal model for studying maternal provisioning, transgenerational epigenetic inheritance, and developmental origins of adult health and disease in humans. This review provides a comprehensive overview of starvation responses throughout the C. elegans life cycle.


Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 825
Author(s):  
Tao Wang ◽  
Robin Gasser

Parasitic nematodes impose a significant public health burden, and cause major economic losses to agriculture worldwide. Due to the widespread of anthelmintic resistance and lack of effective vaccines for most nematode species, there is an urgent need to discover novel therapeutic and vaccine targets, informed through an understanding of host–parasite interactions. Proteomics, underpinned by genomics, enables the global characterisation proteins expressed in a particular cell type, tissue and organism, and provides a key to insights at the host–parasite interface using advanced high-throughput mass spectrometry-based proteomic technologies. Here, we (i) review current mass-spectrometry-based proteomic methods, with an emphasis on a high-throughput ‘bottom-up’ approach; (ii) summarise recent progress in the proteomics of parasitic nematodes of animals, with a focus on molecules inferred to be involved in host–parasite interactions; and (iii) discuss future research directions that could enhance our knowledge and understanding of the molecular interplay between nematodes and host animals, in order to work toward new, improved methods for the treatment, diagnosis and control of nematodiases.


Parasitology ◽  
2009 ◽  
Vol 137 (1) ◽  
pp. 159-171 ◽  
Author(s):  
H. J. McSORLEY ◽  
J. R. GRAINGER ◽  
Y. HARCUS ◽  
J. MURRAY ◽  
A. J. NISBET ◽  
...  

SUMMARYThe transforming growth factor-β (TGF-β) gene family regulates critical processes in animal development, and plays a crucial role in regulating the mammalian immune response. We aimed to identify TGF-β homologues from 2 laboratory model nematodes (Heligmosomoides polygyrus and Nippostrongylus brasiliensis) and 2 major parasites of ruminant livestock (Haemonchus contortus and Teladorsagia circumcincta). Parasite cDNA was used as a template for gene-specific PCR and RACE. Homologues of the TGH-2 subfamily were isolated, and found to differ in length (301, 152, 349 and 305 amino acids respectively), with variably truncated N-terminal pre-proteins. All contained conserved C-terminal active domains (>85% identical over 115 amino acids) containing 9 cysteine residues, as in C. elegans DAF-7, Brugia malayi TGH-2 and mammalian TGF-β. Surprisingly, only the H. contortus homologue retained a conventional signal sequence, absent from shorter proteins of other species. RT-PCR assays of transcription showed that in H. contortus and N. brasiliensis expression was maximal in the infective larval stage, and very low in adult worms. In contrast, in H. polygyrus and T. circumcincta, tgh-2 transcription is higher in adults than infective larvae. The molecular evolution of this gene family in parasitic nematodes has diversified the pre-protein and life-cycle expression patterns of TGF-β homologues while conserving the structure of the active domain.


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1513 ◽  
Author(s):  
Alejandra Wiedeman ◽  
Susan Barr ◽  
Timothy Green ◽  
Zhaoming Xu ◽  
Sheila Innis ◽  
...  

Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and phospholipids; and therefore, choline is involved in a broad range of critical physiological functions across all stages of the life cycle. The current dietary recommendations for choline have been established as Adequate Intakes (AIs) for total choline; however, dietary choline is present in multiple different forms that are both water-soluble (e.g., free choline, phosphocholine, and glycerophosphocholine) and lipid-soluble (e.g., phosphatidylcholine and sphingomyelin). Interestingly, the different dietary choline forms consumed during infancy differ from those in adulthood. This can be explained by the primary food source, where the majority of choline present in human milk is in the water-soluble form, versus lipid-soluble forms for foods consumed later on. This review summarizes the current knowledge on dietary recommendations and assessment methods, and dietary choline intake from food sources across the life cycle.


2020 ◽  
Author(s):  
Martín Klappenbach ◽  
Candela Medina ◽  
Ramiro Freudenthal

AbstractIn the wild, being able to recognize and remember specific locations related to food sources and the associated attributes of landmarks is a cognitive trait important for survival. In the present work we show that the crab Neohelice granulata can be trained to associate a specific environment with an appetitive reward in a conditioned place preference task. After a single training trial, when the crabs were presented with a food pellet in the target quadrant of the training arena, they were able to form a long-term memory related to the event. This memory was evident at least 24 h after training and was protein-synthesis dependent. Importantly, the target area of the arena proved to be a non-neutral environment, given that animals initially avoided the target quadrant. In the present work we introduce for the first time an associative one-trial memory paradigm including a conditioned stimulus with a clear valence performed in a crustacean.


2021 ◽  
Author(s):  
Stephen R Doyle ◽  
Roz Laing ◽  
David Bartley ◽  
Alison Morrison ◽  
Nancy Holroyd ◽  
...  

Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to tracking and combatting their spread. Here, we use a genetic cross in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies novel alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor, cky-1, in ivermectin resistance. This gene is within a locus under selection in ivermectin resistant populations worldwide; functional validation using knockout and gene expression experiments supports a role for cky-1 overexpression in ivermectin resistance. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode, and identifies variants for the development of molecular diagnostics to combat drug resistance in the field.


2020 ◽  
Author(s):  
Nayden Chakarov ◽  
Helge Kampen ◽  
Anja Wiegmann ◽  
Doreen Werner ◽  
Staffan Bensch

Abstract Background: The behaviour of blood-sucking arthropods is a crucial determinant of blood protozoan distribution and hence of host-parasite coevolution, but it is very challenging to study in the wild. The molecular identification of parasite lineages in vectors can be a useful key to understand the behaviour and transmission patterns realised by these vectors. Methods: In this study, we collected blackflies around nests of three raptor species in the upper forest canopy in central Europe and examined the presence of vertebrate DNA and haemosporidian parasites in them. We molecularly analysed 156 blackfly individuals, their vertebrate blood meals, and the haemosporidian parasite lineages they carried. Results: We identified nine species of Simulium blackflies, largely belonging to the subgenera Nevermannia and Eusimulium. Only 1% of the collected specimens was visibly engorged, and only 4% contained remains of host DNA. However, in 29% of the blackflies Leucocytozoon lineages were identified, which is evidence of a previous blood meal on an avian host. Based on the known vertebrate hosts of the recorded Leucocytozoon lineages, we can infer that large and/or abundant birds, such as thrushes, crows, pigeons, birds of prey, owls and tits are the main targets of ornithophilic blackflies in the canopy. Blackfly species contained similar proportions of host group-specific parasite lineages and thus do not appear to be associated with particular host groups. Conclusions: The Leucocytozoon clade infecting thrushes, crows, and pigeons present in most represented blackfly species suggests a lack of association between hosts and blackflies, which can increase the probability of host switches of blood parasites. However, the composition of the simuliid species differed between nests of common buzzards, goshawks and red kites. This segregation can be explained by coinciding habitat preferences between host and vector, and may lead to the fast speciation of Leucocytozoon parasites. Thus, subtle ecological preferences and lack of host preference of vectors in the canopy may enable both parasite diversification and host switches, and enforce a habitat-dependent evolution of avian malaria parasites and related haemosporidia.


2021 ◽  
pp. 270-284
Author(s):  
Regina M. D. G. Carneiro ◽  
Marcilene F. A. Santos ◽  
José Mauro C. Castro

Abstract The following review of the nematodes from cultivated guava is limited to the major problem caused by M. enterolobii, its idenfication and its management strategies. The synonymization of Meloidogyne enterolobii with Meloidogyne mayaguensis and the different methods of identifying Meloidogyne species are discussed. The life cycle, host-parasite relationships, symptoms, damage and dissemination of M. enterolobii are described. The host status of cover crops, maize and fruit plants for M. enterolobii is discussed, as well as the resistance in Psidium spp. to root-knot nematodes. New prospects using genetic resistance in Brazil and some control strategies that can be used in an integrated way are presented.


2021 ◽  
pp. 159-166
Author(s):  
Luis Ernesto Pocasangre Enamorado

Abstract This chapter discusses the economic importance, geographical distribution, host range, damage symptoms, biology and life cycle, interactions with other nematodes and pathogens, recommended integrated management, and management optimization of Radopholus similis infesting bananas. Future research requirements and future developments are also mentioned.


2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Chia-Ni Tsai ◽  
Ting-Chun Pan ◽  
Cho-Han Chiang ◽  
Chun-Chiao Yu ◽  
Shih-Han Su ◽  
...  

ABSTRACT The nonstructural protein NS5A of hepatitis C virus (HCV) is a phosphorylated protein that is indispensable for viral replication and assembly. We previously showed that NS5A undergoes sequential serine S232/S235/S238 phosphorylation resulting in NS5A transition from a hypo- to a hyperphosphorylated state. Here, we studied functions of S229 with a newly generated antibody specific to S229 phosphorylation. In contrast to S232, S235, or S238 phosphorylation detected only in the hyperphosphorylated NS5A, S229 phosphorylation was found in both hypo- and hyperphosphorylated NS5A, suggesting that S229 phosphorylation initiates NS5A sequential phosphorylation. Immunoblotting showed an inverse relationship between S229 phosphorylation and S235 phosphorylation. When S235 was phosphorylated as in the wild-type NS5A, the S229 phosphorylation level was low; when S235 could not be phosphorylated as in the S235A mutant NS5A, the S229 phosphorylation level was high. These results suggest an intrinsic feedback regulation between S229 phosphorylation and S235 phosphorylation. It has been known that NS5A distributes in large static and small dynamic intracellular structures and that both structures are required for the HCV life cycle. We found that S229A or S229D mutation was lethal to the virus and that both increased NS5A in large intracellular structures. Similarly, the lethal S235A mutation also increased NS5A in large structures. Likewise, the replication-compromised S235D mutation also increased NS5A in large structures, albeit to a lesser extent. Our data suggest that S229 probably cycles through phosphorylation and dephosphorylation to maintain a delicate balance of NS5A between hypo- and hyperphosphorylated states and the intracellular distribution necessary for the HCV life cycle. IMPORTANCE This study joins our previous efforts to elucidate how NS5A transits between hypo- and hyperphosphorylated states via phosphorylation on a series of highly conserved serine residues. Of the serine residues, serine 229 is the most interesting since phosphorylation-mimicking and phosphorylation-ablating mutations at this serine residue are both lethal. With a new high-quality antibody specific to serine 229 phosphorylation, we concluded that serine 229 must remain wild type so that it can dynamically cycle through phosphorylation and dephosphorylation that govern NS5A between hypo- and hyperphosphorylated states. Both are required for the HCV life cycle. When phosphorylated, serine 229 signals phosphorylation on serine 232 and 235 in a sequential manner, leading NS5A to the hyperphosphorylated state. As serine 235 phosphorylation is reached, serine 229 is dephosphorylated, stopping signal for hyperphosphorylation. This balances NS5A between two phosphorylation states and in intracellular structures that warrant a productive HCV life cycle.


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