scholarly journals Symbiosis Comes of Age at the 10th Biennial Meeting of Wolbachia Researchers

2019 ◽  
Vol 85 (8) ◽  
Author(s):  
Irene L. G. Newton ◽  
Barton E. Slatko
Keyword(s):  
Cell Biology ◽  
Rna Virus ◽  
Host Cells ◽  
Human Pathogens ◽  
Content Type ◽  
New Science ◽  
Successful Infection ◽  
Filarial Nematodes ◽  
Insect Populations ◽  
Basic Biology

ABSTRACT Wolbachia pipientis is an alphaproteobacterial obligate intracellular microbe and arguably the most successful infection on our planet, colonizing 40% to 60% of insect species. Wolbachia spp. are also present in most, but not all, filarial nematodes, where they are obligate mutualists and are the targets for antifilarial drug discovery. Although Wolbachia spp. are related to important human pathogens, they do not infect mammals but instead are well known for their reproductive manipulations of insect populations, inducing the following phenotypes: male killing, feminization, parthenogenesis induction, and cytoplasmic incompatibility (CI). The most common of these, CI, results in a sperm-egg incompatibility and increases the relative fecundity of infected females in a population. In the last decade, Wolbachia spp. have also been shown to provide a benefit to insects, where the infection can inhibit RNA virus replication within the host. Wolbachia spp. cannot be cultivated outside host cells, and no genetic tools are available in the symbiont, limiting approaches available for their study. This means that many questions fundamental to our understanding of Wolbachia basic biology remained unknown for decades. The 10th biennial international Wolbachia conference, Wolbachia Evolution, Ecology, Genomics and Cell Biology: A Chronicle of the Most Ubiquitous Symbiont, was held on 17 to 22 June 2018 in Salem, MA. In this review, we highlight the new science presented at the meeting, link it to prior efforts to answer these questions across the Wolbachia genus, and present the importance of these findings to the field of symbiosis. The topics covered in this review are based on the presentations at the conference.

Basic Biology of Trypanosoma Cruzi

2020 ◽  
Vol 26 ◽  
Author(s):  
Aline Araujo Zuma ◽  
Emile dos Santos Barrias ◽  
Wanderley de Souza
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Cell Biology ◽  
Structural Organization ◽  
Developmental Stages ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Cellular Organization ◽  
Basic Biology ◽  
Comparative Information

Abstract:: The present review addresses basic aspects of the biology of the pathogenic protozoa Trypanosoma cruzi and some comparative information with Trypanosoma brucei. Like eukaryotic cells, their cellular organization is similar to that of mammalian hosts. However, these parasites present structural particularities. That is why the following topics are emphasized in this paper: developmental stages of the life cycle in the vertebrate and invertebrate hosts; the cytoskeleton of the protozoa, especially the sub-pellicular microtubules; the flagellum and its attachment to the protozoan body through specialized junctions; the kinetoplast-mitochondrion complex, including its structural organization and DNA replication; the glycosome and its role in the metabolism of the cell; the acidocalcisome, describing its morphology, biochemistry, and functional role; the cytostome and the endocytic pathway; the organization of the endoplasmic reticulum and Golgi complex; the nucleus, describing its structural organization during interphase and division; and the process of interaction of the parasite with host cells. The unique characteristics of these structures also make them interesting chemotherapeutic targets. Therefore, further understanding of cell biology aspects contributes to the development of drugs for chemotherapy.

scholarly journals Enteropathogenic Escherichia coli and Vaccinia Virus Do Not Require the Family of WASP-Interacting Proteins for Pathogen-Induced Actin Assembly

2012 ◽  
Vol 80 (12) ◽  
pp. 4071-4077 ◽  
Author(s):  
John J. Garber ◽  
Fuminao Takeshima ◽  
Inés M. Antón ◽  
Michiko K. Oyoshi ◽  
Anna Lyubimova ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Vaccinia Virus ◽  
Family Members ◽  
Ectopic Expression ◽  
Host Cells ◽  
Actin Assembly ◽  
Human Pathogens ◽  
Interacting Protein ◽  
Content Type ◽  
Syndrome Protein

ABSTRACTThe human pathogens enteropathogenicEscherichia coli(EPEC) and vaccinia virus trigger actin assembly in host cells by activating the host adaptor Nck and the actin nucleation promoter neural Wiskott-Aldrich syndrome protein (N-WASP). EPEC translocates effector molecules into host cells via type III secretion, and the interaction between the translocated intimin receptor (Tir) and the bacterial membrane protein intimin stimulates Nck and N-WASP recruitment, leading to the formation of actin pedestals beneath adherent bacteria. Vaccinia virus also recruits Nck and N-WASP to generate actin tails that promote cell-to-cell spread of the virus. In addition to Nck and N-WASP, WASP-interacting protein (WIP) localizes to vaccinia virus tails, and inhibition of actin tail formation upon ectopic expression of WIP mutants led to the suggestion that WIP is required for this process. Similar studies of WIP mutants, however, did not affect the ability of EPEC to form actin pedestals, arguing against an essential role for WIP in EPEC-induced actin assembly. In this study, we demonstrate that Nck and N-WASP are normally recruited by vaccinia virus and EPEC in the absence of WIP, and neither WIP nor the WIP family members CR16 and WIRE/WICH are essential for pathogen induced actin assembly. In addition, although Nck binds EPEC Tir directly, N-WASP is required for its localization during pedestal formation. Overall, these data highlight similar pathogenic strategies shared by EPEC and vaccinia virus by demonstrating a requirement for both Nck and N-WASP, but not WIP or WIP family members in pathogen-induced actin assembly.

scholarly journals Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Tadakimi Tomita ◽  
Hua Wang ◽  
Peng Wu ◽  
Louis M. Weiss
Keyword(s):  
Toxoplasma Gondii ◽  
Small Molecules ◽  
Click Chemistry ◽  
Cell Biology ◽  
Host Cells ◽  
Intracellular Parasite ◽  
Content Type ◽  
Intracellular Parasites ◽  
Specific Manner ◽  
Selective Delivery

ABSTRACT Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population. The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis. The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans. In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites. We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells. Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner. IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells. We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology. This system provides a valuable tool for studying many intracellular parasites.

scholarly journals Capsid Structure of a Marine Algal Virus of the Order Picornavirales

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Anna Munke ◽  
Kei Kimura ◽  
Yuji Tomaru ◽  
Kenta Okamoto
Keyword(s):  
Structural Changes ◽  
Rna Virus ◽  
Structural Features ◽  
Human Pathogens ◽  
Receptor Binding Site ◽  
Content Type ◽  
Domain Swap ◽  
Algal Virus ◽  
Structural Traits ◽  
Marine Algal

ABSTRACT The order Picornavirales includes viruses that infect different kinds of eukaryotes and that share similar properties. The capsid proteins (CPs) of viruses in the order that infect unicellular organisms, such as algae, presumably possess certain characteristics that have changed little over the course of evolution, and thus these viruses may resemble the Picornavirales ancestor in some respects. Herein, we present the capsid structure of Chaetoceros tenuissimus RNA virus type II (CtenRNAV-II) determined using cryo-electron microscopy at a resolution of 3.1 Å, the first alga virus belonging to the family Marnaviridae of the order Picornavirales. A structural comparison to related invertebrate and vertebrate viruses revealed a unique surface loop of the major CP VP1 that had not been observed previously, and further, revealed that another VP1 loop obscures the so-called canyon, which is a host-receptor binding site for many of the mammalian Picornavirales viruses. VP2 has an N-terminal tail, which has previously been reported as a primordial feature of Picornavirales viruses. The above-mentioned and other critical structural features provide new insights on three long-standing theories about Picornavirales: (i) the canyon hypothesis, (ii) the primordial VP2 domain swap, and (iii) the hypothesis that alga Picornavirales viruses could share characteristics with the Picornavirales ancestor. IMPORTANCE Identifying the acquired structural traits in virus capsids is important for elucidating what functions are essential among viruses that infect different hosts. The Picornavirales viruses infect a broad spectrum of hosts, ranging from unicellular algae to insects and mammals and include many human pathogens. Those viruses that infect unicellular protists, such as algae, are likely to have undergone fewer structural changes during the course of evolution compared to those viruses that infect multicellular eukaryotes and thus still share some characteristics with the Picornavirales ancestor. This article describes the first atomic capsid structure of an alga Marnavirus, CtenRNAV-II. A comparison to capsid structures of the related invertebrate and vertebrate viruses identified a number of structural traits that have been functionally acquired or lost during the course of evolution. These observations provide new insights on past theories on the viability and evolution of Picornavirales viruses.

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.

scholarly journals An in silico map of the SARS-CoV-2 RNA Structurome

2020 ◽  
Author(s):  
Ryan J. Andrews ◽  
Jake M. Peterson ◽  
Hafeez S. Haniff ◽  
Jonathan Chen ◽  
Christopher Williams ◽  
...  
Keyword(s):  
Small Molecules ◽  
Rna Structure ◽  
Drug Targets ◽  
Rna Binding ◽  
Rna Virus ◽  
Human Pathogens ◽  
Public Database ◽  
Positive Sense ◽  
Basic Biology ◽  
Potential Drug Targets

AbstractSARS-CoV-2 is a positive-sense single-stranded RNA virus that has exploded throughout the global human population. This pandemic coronavirus strain has taken scientists and public health researchers by surprise and knowledge of its basic biology (e.g. structure/function relationships in its genomic, messenger and template RNAs) and modes for therapeutic intervention lag behind that of other human pathogens. In this report we used a recently-developed bioinformatics approach, ScanFold, to deduce the RNA structural landscape of the SARS-CoV-2 transcriptome. We recapitulate known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that the SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a huge reservoir of potential drug targets for RNA-binding small molecules. Our results also predict regions that are accessible for intermolecular interactions, which can aid in the design of antisense therapeutics. All results are made available via a public database (the RNAStructuromeDB) where they may hopefully drive drug discovery efforts to inhibit SARS-CoV-2 pathogenesis.

scholarly journals Differential Impacts on Host Transcription by ROP and GRA Effectors from the Intracellular Parasite Toxoplasma gondii

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Suchita Rastogi ◽  
Yuan Xue ◽  
Stephen R. Quake ◽  
John C. Boothroyd
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Biology ◽  
Parasitophorous Vacuole ◽  
Effector Proteins ◽  
Transcriptomic Analysis ◽  
Host Cells ◽  
Intracellular Parasite ◽  
Content Type ◽  
I Cells

ABSTRACT The intracellular parasite Toxoplasma gondii employs a vast array of effector proteins from the rhoptry and dense granule organelles to modulate host cell biology; these effectors are known as ROPs and GRAs, respectively. To examine the individual impacts of ROPs and GRAs on host gene expression, we developed a robust, novel protocol to enrich for ultrapure populations of a naturally occurring and reproducible population of host cells called uninfected-injected (U-I) cells, which Toxoplasma injects with ROPs but subsequently fails to invade. We then performed single-cell transcriptomic analysis at 1 to 3 h postinfection on U-I cells (as well as on uninfected and infected controls) arising from infection with either wild-type parasites or parasites lacking the MYR1 protein, which is required for soluble GRAs to cross the parasitophorous vacuole membrane (PVM) and reach the host cell cytosol. Based on comparisons of infected and U-I cells, the host’s earliest response to infection appears to be driven primarily by the injected ROPs, which appear to induce immune and cellular stress pathways. These ROP-dependent proinflammatory signatures appear to be counteracted by at least some of the MYR1-dependent GRAs and may be enhanced by the MYR-independent GRAs (which are found embedded within the PVM). Finally, signatures detected in uninfected bystander cells from the infected monolayers suggest that MYR1-dependent paracrine effects also counteract inflammatory ROP-dependent processes. IMPORTANCE This work performs transcriptomic analysis of U-I cells, captures the earliest stage of a host cell’s interaction with Toxoplasma gondii, and dissects the effects of individual classes of parasite effectors on host cell biology.

scholarly journals The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae

2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Yaohua Zhu ◽  
Yan Wu ◽  
Yan Chai ◽  
Jianxun Qi ◽  
Ruchao Peng ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Fusion Protein ◽  
Protein Conformation ◽  
Fusion Proteins ◽  
Taxonomic Revision ◽  
Class Ii ◽  
Viral Envelope ◽  
Host Cells ◽  
Human Pathogens ◽  
Content Type

ABSTRACT Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales. Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection. HRTV delivers its genome into the cytoplasm by fusion of the viral envelope and endosomal membranes under low-pH conditions. Here, we describe the crystal structure of HRTV Gc in its postfusion conformation. The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family. However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation. This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses. Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens. IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans. It belongs to the newly defined family Phenuiviridae, order Bunyavirales. HRTV contains three single-stranded RNA segments (L, M, and S). The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc. Gc is a fusion protein facilitating virus entry into host cells. Here, we report the crystal structure of the HRTV Gc protein. The structure displays a typical class II fusion protein conformation. Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses. Our results expand the knowledge of bunyavirus fusion proteins and help us to understand bunyavirus characterizations. This study provides useful information to improve protection against and therapies for bunyavirus infections.

scholarly journals Engineered Liposomes Protect Immortalized Immune Cells from Cytolysins Secreted by Group A and Group G Streptococci

Cells ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 166
Author(s):  
Hervé Besançon ◽  
Yu Larpin ◽  
Viktoria S. Babiychuk ◽  
René Köffel ◽  
Eduard B. Babiychuk
Keyword(s):  
Immune Cells ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Host Cells ◽  
Human Pathogens ◽  
Efficient Treatment ◽  
Group G Streptococci ◽  
Cell Plasma ◽  
Successful Infection ◽  
Life Threatening

The increasing antibiotic resistance of bacterial pathogens fosters the development of alternative, non-antibiotic treatments. Antivirulence therapy, which is neither bacteriostatic nor bactericidal, acts by depriving bacterial pathogens of their virulence factors. To establish a successful infection, many bacterial pathogens secrete exotoxins/cytolysins that perforate the host cell plasma membrane. Recently developed liposomal nanotraps, mimicking the outer layer of the targeted cell membranes, serve as decoys for exotoxins, thus diverting them from attacking host cells. In this study, we develop a liposomal nanotrap formulation that is capable of protecting immortalized immune cells from the whole palette of cytolysins secreted by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis—important human pathogens that can cause life-threatening bacteremia. We show that the mixture of cholesterol-containing liposomes with liposomes composed exclusively of phospholipids is protective against the combined action of all streptococcal exotoxins. Our findings pave the way for further development of liposomal antivirulence therapy in order to provide more efficient treatment of bacterial infections, including those caused by antibiotic resistant pathogens.

scholarly journals Time-resolved transcriptional profiling of Trichinella-infected murine myocytes helps to elucidate host–pathogen interactions in the muscle stage

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoxiang Hu ◽  
Xiaolei Liu ◽  
Chen Li ◽  
Yulu Zhang ◽  
Chengyao Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Biology ◽  
Trichinella Spiralis ◽  
Expression Patterns ◽  
Muscle Cells ◽  
Host Cells ◽  
Initial Reaction ◽  
Global Changes ◽  
Mammalian Skeletal Muscle ◽  
Time Resolved

Abstract Background Parasites of the genus Trichinella are the pathogenic agents of trichinellosis, which is a widespread and severe foodborne parasitic disease. Trichinella spiralis resides primarily in mammalian skeletal muscle cells. After invading the cells of the host organism, T. spiralis must elude or invalidate the host’s innate and adaptive immune responses to survive. It is necessary to characterize the pathogenesis of trichinellosis to help to prevent the occurrence and further progression of this disease. The aims of this study were to elucidate the mechanisms of nurse cell formation, pathogenesis and immune evasion of T. spiralis, to provide valuable information for further research investigating the basic cell biology of Trichinella-infected muscle cells and the interaction between T. spiralis and its host. Methods We performed transcriptome profiling by RNA sequencing to identify global changes at 1, 3, 7, 10 and 15 days post-infection (dpi) in gene expression in the diaphragm after the parasite entered and persisted within the murine myocytes; the mice were infected by intravenous injection of newborn larvae. Gene expression analysis was based on the alignment results. Differentially expressed genes (DEGs) were identified based on their expression levels in various samples, and functional annotation and enrichment analysis were performed. Results The most extensive and dynamic gene expression responses in host diaphragms were observed during early infection (1 dpi). The number of DEGs and genes annotated in the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases decreased significantly in the infected mice compared to the uninfected mice at 3 and 7 dpi, suddenly increased sharply at 10 dpi, and then decreased to a lower level at 15 dpi, similar to that observed at 3 and 7 dpi. The massive initial reaction of the murine muscle cells to Trichinella infection steadied in the later stages of infection, with little additional changes detected for the remaining duration of the studied process. Although there were hundreds of DEGs at each time point, only 11 genes were consistently up- or downregulated at all 5 time points. Conclusions The gene expression patterns identified in this study can be employed to characterize the coordinated response of T. spiralis-infected myocytes in a time-resolved manner. This comprehensive dataset presents a distinct and sensitive picture of the interaction between host and parasite during intracellular infection, which can help to elucidate how pathogens evade host defenses and coordinate the biological functions of host cells to survive in the mammalian environment.

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