scholarly journals Special Issue: “Viral Replication Complexes”

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1902
Author(s):  
Núria Verdaguer ◽  
Diego S. Ferrero
Keyword(s):  
Viral Replication ◽  
Special Issue ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Biological Entities ◽  
Cellular Components

Viruses are extraordinary biological entities that can only thrive as obligate intracellular parasites, exploiting other living cellular components in order to reproduce [...]

scholarly journals Muller’s Ratchet and Ribosome Degeneration in the Obligate Intracellular Parasites Microsporidia

2018 ◽  
Vol 19 (12) ◽  
pp. 4125 ◽  
Author(s):  
Sergey Melnikov ◽  
Kasidet Manakongtreecheep ◽  
Keith Rivera ◽  
Arthur Makarenko ◽  
Darryl Pappin ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Evolutionary Process ◽  
Obligate Intracellular ◽  
Muller's Ratchet ◽  
Automated Annotation ◽  
Intracellular Parasites ◽  
Genome Decay ◽  
Muller’S Ratchet ◽  
Forms Of Life ◽  
Cellular Components

Microsporidia are fungi-like parasites that have the smallest known eukaryotic genome, and for that reason they are used as a model to study the phenomenon of genome decay in parasitic forms of life. Similar to other intracellular parasites that reproduce asexually in an environment with alleviated natural selection, Microsporidia experience continuous genome decay that is driven by Muller’s ratchet—an evolutionary process of irreversible accumulation of deleterious mutations that lead to gene loss and the miniaturization of cellular components. Particularly, Microsporidia have remarkably small ribosomes in which the rRNA is reduced to the minimal enzymatic core. In this study, we analyzed microsporidian ribosomes to study an apparent impact of Muller’s ratchet on structure of RNA and protein molecules in parasitic forms of life. Through mass spectrometry of microsporidian proteome and analysis of microsporidian genomes, we found that massive rRNA reduction in microsporidian ribosomes appears to annihilate the binding sites for ribosomal proteins eL8, eL27, and eS31, suggesting that these proteins are no longer bound to the ribosome in microsporidian species. We then provided an evidence that protein eS31 is retained in Microsporidia due to its non-ribosomal function in ubiquitin biogenesis. Our study illustrates that, while Microsporidia carry the same set of ribosomal proteins as non-parasitic eukaryotes, some ribosomal proteins are no longer participating in protein synthesis in Microsporidia and they are preserved from genome decay by having extra-ribosomal functions. More generally, our study shows that many components of parasitic cells, which are identified by automated annotation of pathogenic genomes, may lack part of their biological functions due to continuous genome decay.

Antiphage activity of natural and synthetic substances: a new age for antivirals?

2020 ◽  
Vol 15 (9) ◽  
pp. 767-777
Author(s):  
Jhonatan M Ribeiro ◽  
Giovana N Pereira ◽  
Renata KT Kobayashi ◽  
Gerson Nakazato
Keyword(s):  
Mammalian Cells ◽  
Eukaryotic Cell ◽  
Future Perspective ◽  
Viral Diseases ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
A Genome ◽  
Living Organisms ◽  
Biological Entities ◽  
Antiphage Activity

Viruses are considered biological entities that possess a genome and can adapt to the environment of living organisms. Since they are obligate intracellular parasites, their cycle of replication can result in cell death, and consequently, some viruses are harmful to mammalian cells and can cause disease in humans. Therefore, the search for substances for the treatment of viral diseases can be accomplished through the use of bacteriophages as models for eukaryotic cell viruses. Thus, this review highlights the main studies identifying substances with antiphage activity in comparison assays involving phages and eukaryotic viruses, in order to explore the potential of these substances as antivirals. As a future perspective, this approach may help at the beginning of an Antiviral Age.

scholarly journals Sphingolipids: Effectors and Achilles Heals in Viral Infections?

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2175
Author(s):  
Sibylle Schneider-Schaulies ◽  
Fabian Schumacher ◽  
Dominik Wigger ◽  
Marie Schöl ◽  
Trushnal Waghmare ◽  
...  
Keyword(s):  
Life Cycle ◽  
Viral Replication ◽  
Viral Infections ◽  
Cellular Level ◽  
Host Cells ◽  
Cellular Membranes ◽  
Replication Process ◽  
Intracellular Parasites ◽  
Intracellular Compartments ◽  
Cellular Components

As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.

scholarly journals Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma gondii

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 476
Author(s):  
Joachim Kloehn ◽  
Matteo Lunghi ◽  
Emmanuel Varesio ◽  
David Dubois ◽  
Dominique Soldati-Favre
Keyword(s):  
Amino Acids ◽  
Toxoplasma Gondii ◽  
Rna Degradation ◽  
Major Facilitator Superfamily ◽  
Untargeted Metabolomics ◽  
Apicomplexan Parasites ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Major Facilitator ◽  
Plasma Membrane Transporter

Apicomplexan parasites are responsible for devastating diseases, including malaria, toxoplasmosis, and cryptosporidiosis. Current treatments are limited by emerging resistance to, as well as the high cost and toxicity of existing drugs. As obligate intracellular parasites, apicomplexans rely on the uptake of many essential metabolites from their host. Toxoplasma gondii, the causative agent of toxoplasmosis, is auxotrophic for several metabolites, including sugars (e.g., myo-inositol), amino acids (e.g., tyrosine), lipidic compounds and lipid precursors (cholesterol, choline), vitamins, cofactors (thiamine) and others. To date, only few apicomplexan metabolite transporters have been characterized and assigned a substrate. Here, we set out to investigate whether untargeted metabolomics can be used to identify the substrate of an uncharacterized transporter. Based on existing genome- and proteome-wide datasets, we have identified an essential plasma membrane transporter of the major facilitator superfamily in T. gondii—previously termed TgApiAT6-1. Using an inducible system based on RNA degradation, TgApiAT6-1 was depleted, and the mutant parasite’s metabolome was compared to that of non-depleted parasites. The most significantly reduced metabolite in parasites depleted in TgApiAT6-1 was identified as the amino acid lysine, for which T. gondii is predicted to be auxotrophic. Using stable isotope-labeled amino acids, we confirmed that TgApiAT6-1 is required for efficient lysine uptake. Our findings highlight untargeted metabolomics as a powerful tool to identify the substrate of orphan transporters.

Encystment and germination of the parasitic chytrid Rozella allomycis on host hyphae

1973 ◽  
Vol 51 (10) ◽  
pp. 1825-1835 ◽  
Author(s):  
Abraham A. Held
Keyword(s):  
Cyst Wall ◽  
Germ Tube ◽  
Light And Electron Microscopy ◽  
Multivesicular Bodies ◽  
Cell Periphery ◽  
General Sequence ◽  
Obligate Intracellular ◽  
Host Cytoplasm ◽  
Intracellular Parasites ◽  
Three Stages

Zoospores of the obligately parasitic chytrid Rozella allomycis which settle upon hyphae of the water mold host, Allomyces arbuscula, encyst and germinate before their protoplasts penetrate into the host cytoplasm. This process has been examined by light and electron microscopy. Three stages which follow the attachment to the host and the retraction of the zoospore's flagellum are described: (1) the early cyst lacks a wall; it is discoid, and its shape is maintained by the coil of the retracted axoneme which forms its rim; (2) a cyst wall is formed while multivesicular bodies occur at the cell periphery and eventually disappear; a germ tube starts to grow at the point of attachment; and (3) the firm-walled cyst is spheroidal; it has a fully developed germ tube with a specialized class of vesicles; it also forms a distal, flattened vacuole whose swelling eventually injects the Rozella protoplast into the host; at this stage the retracted axoneme has disappeared and the cell's organelles have undergone extensive changes. Electron-dense, "gamma-like" granules enclosed in vacuoles may play a major role in the formation of both the cyst wall and the distal vacuole. These granules appear to give rise to small vesicles, and thus to multivesicular bodies; the distal vacuole appears to form by coalescense of gamma-like vacuoles.The general sequence of encystment and germination resembles that found in other Chytridiomycetes, both saprophytic and parasitic. However, the distal vacuole and the vesicles in the germ tube appear to be parasitic adaptations and are shared by obligate intracellular parasites from several unrelated groups of zoosporic fungi.

Round Table Discussion

PEDIATRICS ◽  
1948 ◽  
Vol 2 (4) ◽  
pp. 469-479
Author(s):  
RUSSELL J. BLATTNER
Keyword(s):  
Inclusion Bodies ◽  
Cellular Response ◽  
Infectious Agent ◽  
Round Table ◽  
Chemotherapeutic Agents ◽  
Tissue Response ◽  
Round Table Discussion ◽  
Obligate Intracellular ◽  
Form Of Life ◽  
Intracellular Parasites

Chairman Blattner: During recent years, there has been increasing interest shown in diseases caused by filterable viruses, and significant work has been accomplished in this comparatively new and absorbing field of endeavor. With the advent of chemotherapeutic agents and antibiotics, the presence and action of these infectious agents has become more apparent. Viral diseases, therefore, have assumed increasing importance in medical literature in general and in pediatric literature in particular. By way of review, it is well to bear in mind that viruses are filter-passing agents, obligate intracellular parasites, capable of reproducing themselves and of producing disease in plants and animals, including man. While these agents cannot be seen except by the most elaborate methods, their presence can be detected by their injurious effects. The pathologic picture produced by viral agents is rather characteristic and can be recognized readily by experienced observers acquainted with tissue response. In some instances, inclusion bodies are produced which may be intranuclear or intracytoplasmic, and represent cytologic changes which are considered typical of the pathologic response to viral invasion. When inclusion bodies are present they may serve as sign posts for the recognition of the type of infectious agent. The nature of a filterable virus is as yet unknown. Viruses may be a form of life similar to bacteria, but infinitely smaller in size. It is conceivable that viruses are enzymes capable of reproducing themselves and capable of producing cellular response. They may be non-living, crystallizable substances, such as the Stanley tobacco-mosaic virus; or a form of life, the definite nature of which is as yet unrecognized. Dr. Thomas M. Rivers has stated : "Viruses are a heterogeneous collection of diverse agents which happen to induce a state of broad similarity." He points out that the reaction of the tissues in general, and of the cells in particular, determines the nature of the pathologic process about as much as the infectious agent itself.

scholarly journals A metabolic dependency for host isoprenoids in the obligate intracellular pathogenRickettsia parkeriunderlies a sensitivity for the statin class of host-targeted therapeutics

2019 ◽  
Author(s):  
Vida Ahyong ◽  
Charles A. Berdan ◽  
Daniel K. Nomura ◽  
Matthew D. Welch
Keyword(s):  
Cell Wall ◽  
Host Cell ◽  
Bacterial Growth ◽  
Spotted Fever ◽  
Intracellular Pathogens ◽  
Biosynthetic Pathways ◽  
Targeted Therapeutics ◽  
Rickettsia Parkeri ◽  
Obligate Intracellular ◽  
Intracellular Parasites

AbstractGram-negative bacteria in the order Rickettsiales are obligate intracellular parasites that cause human diseases such typhus and spotted fever. They have evolved a dependence on essential nutrients and metabolites from the host cell as a consequence of extensive genome streamlining. However, it remains largely unknown which nutrients they require and whether their metabolic dependency can be exploited therapeutically. Here, we describe a genetic rewiring of bacterial isoprenoid biosynthetic pathways in the Rickettsiales that has resulted from reductive genome evolution. We further investigated whether the spotted fever groupRickettsiaspeciesRickettsia parkeriscavenges isoprenoid precursors directly from the host. Using targeted mass spectrometry in uninfected and infected cells, we found decreases in host isoprenoid products and concomitant increases in bacterial isoprenoid metabolites. Additionally, we report that bacterial growth is prohibited by inhibition of the host isoprenoid pathway with the statins class of drugs. We show that growth inhibition correlates with changes in bacterial size and shape that mimic those caused by antibiotics that inhibit peptidoglycan biosynthesis, suggesting statins inhibit cell wall synthesis. Altogether, our results describe an Achilles’ heel of obligate intracellular pathogens that can be exploited with host-targeted therapeutics that interfere with metabolic pathways required for bacterial growth.ImportanceObligate intracellular parasites, which include viruses as well as certain bacteria and eukaryotes, extract essential nutrients and metabolites from their host cell. As a result, these pathogens have often lost essential biosynthetic pathways and are metabolically dependent on the host. In this study, we describe a metabolic dependency of the bacterial pathogenRickettsia parkerion host isoprenoid molecules that are used in the biosynthesis of downstream products including cholesterol, steroid hormones, and heme. Bacteria make products from isoprenoids such as an essential lipid carrier for making the bacterial cell wall. We show that bacterial metabolic dependency can represent an Achilles’ heel, and that inhibiting host isoprenoid biosynthesis with the FDA-approved statin class of drugs inhibits bacterial growth by interfering with the integrity of the cell wall. This work highlights a potential to treat infections by obligate intracellular pathogens through inhibition of host biosynthetic pathways that are susceptible to parasitism.

Subversion of host cell signalling by the protozoan parasiteLeishmania

Parasitology ◽  
2005 ◽  
Vol 130 (S1) ◽  
pp. S27-S35 ◽  
Author(s):  
D. J. GREGORY ◽  
M. OLIVIER
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Cell Signalling ◽  
Protein Tyrosine Phosphatases ◽  
Innate Immune ◽  
Signalling Pathways ◽  
Oxygen Species ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Intracellular Ca

The protozoaLeishmaniaspp. are obligate intracellular parasites that inhabit the macrophages of their host. Since macrophages are specialized for the identification and destruction of invading pathogens, both directly and by triggering an innate immune response,Leishmaniahave evolved a number of mechanisms for suppressing some critical macrophage activities. In this review, we discuss how various species ofLeishmaniadistort the host macrophage's own signalling pathways to repress the expression of various cytokines and microbicidal molecules (nitric oxide and reactive oxygen species), and antigen presentation. In particular, we describe how MAP Kinase and JAK/STAT cascades are repressed, and intracellular Ca2+and the activities of protein tyrosine phosphatases, in particular SHP-1, are elevated.

scholarly journals Suicidal Leishmania

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 79 ◽  
Author(s):  
Lucie Podešvová ◽  
Tereza Leštinová ◽  
Eva Horáková ◽  
Julius Lukeš ◽  
Petr Volf ◽  
...  
Keyword(s):  
Cell Death ◽  
Phospholipase A2 ◽  
Cutaneous Leishmaniasis ◽  
Human Pathogen ◽  
Leishmania Mexicana ◽  
Macrophage Infection ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Tropical Infections

Leishmania are obligate intracellular parasites known to have developed successful ways of efficient immunity evasion. Because of this, leishmaniasis, a disease caused by these flagellated protists, is ranked as one of the most serious tropical infections worldwide. Neither prophylactic medication, nor vaccination has been developed thus far, even though the infection has usually led to strong and long-lasting immunity. In this paper, we describe a “suicidal” system established in Leishmania mexicana, a human pathogen causing cutaneous leishmaniasis. This system is based on the expression and (de)stabilization of a basic phospholipase A2 toxin from the Bothrops pauloensis snake venom, which leads to the inducible cell death of the parasites in vitro. Furthermore, the suicidal strain was highly attenuated during macrophage infection, regardless of the toxin stabilization. Such a deliberately weakened parasite could be used to vaccinate the host, as its viability is regulated by the toxin stabilization, causing a profoundly reduced pathogenesis.

scholarly journals Single cell ecology

2019 ◽  
Vol 374 (1786) ◽  
pp. 20190076 ◽  
Author(s):  
Thomas A. Richards ◽  
Ramon Massana ◽  
Stefano Pagliara ◽  
Neil Hall
Keyword(s):  
Single Cell ◽  
Building Blocks ◽  
Biological Properties ◽  
Natural Environments ◽  
Biological Processes ◽  
Special Issue ◽  
New Approaches ◽  
New Methodologies ◽  
Biological Entities ◽  
The Way

Cells are the building blocks of life, from single-celled microbes through to multi-cellular organisms. To understand a multitude of biological processes we need to understand how cells behave, how they interact with each other and how they respond to their environment. The use of new methodologies is changing the way we study cells allowing us to study them on minute scales and in unprecedented detail. These same methods are allowing researchers to begin to sample the vast diversity of microbes that dominate natural environments. The aim of this special issue is to bring together research and perspectives on the application of new approaches to understand the biological properties of cells, including how they interact with other biological entities. This article is part of a discussion meeting issue ‘Single cell ecology’.

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