bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative Stress Correlates with Wolbachia-Mediated Antiviral Protection in Wolbachia-Drosophila Associations
Authors: Wong Zhee Sheen , Brownlie Jeremy C. , Johnson Karyn N. 
Published: February 2015

ABSTRACT

Wolbachia
mediates antiviral protection in insect hosts and is being developed as a potential biocontrol agent to reduce the spread of insect-vectored viruses. Definition of the molecular mechanism that generates protection is important for understanding the tripartite interaction between host insect,
Wolbachia
, and virus. Elevated oxidative stress was previously reported for a mosquito line experimentally infected with
Wolbachia
, suggesting that oxidative stress is important for
Wolbachia
-mediated antiviral protection. However,
Wolbachia
experimentally introduced into mosquitoes impacts a range of host fitness traits, some of which are unrelated to antiviral protection. To explore whether elevated oxidative stress is associated with antiviral protection in
Wolbachia
-infected insects, we analyzed oxidative stress of five
Wolbachia
-infected
Drosophila
lines. In flies infected with protective
Wolbachia
strains, hydrogen peroxide concentrations were 1.25- to 2-fold higher than those in paired fly lines cured of
Wolbachia
infection. In contrast, there was no difference in the hydrogen peroxide concentrations in flies infected with nonprotective
Wolbachia
strains compared to flies cured of
Wolbachia
infection. Using a
Drosophila
mutant that produces increased levels of hydrogen peroxide, we investigated whether flies with high levels of endogenous reactive oxygen species had altered responses to virus infection and found that flies with high levels of endogenous hydrogen peroxide were less susceptible to virus-induced mortality. Taken together, these results suggest that elevated oxidative stress correlates with
Wolbachia
-mediated antiviral protection in natural
Drosophila
hosts.
Responses of Yeast Biocontrol Agents to Environmental Stress
Authors: Sui Yuan , Wisniewski Michael , Droby Samir , Liu Jia 
Published: February 2015

ABSTRACT
Biological control of postharvest diseases, utilizing wild species and strains of antagonistic yeast species, is a research topic that has received considerable attention in the literature over the past 30 years. In principle, it represents a promising alternative to chemical fungicides for the management of postharvest decay of fruits, vegetables, and grains. A yeast-based biocontrol system is composed of a tritrophic interaction between a host (commodity), a pathogen, and a yeast species, all of which are affected by environmental factors such as temperature, pH, and UV light as well as osmotic and oxidative stresses. Additionally, during the production process, biocontrol agents encounter various severe abiotic stresses that also impact their viability. Therefore, understanding the ecological fitness of the potential yeast biocontrol agents and developing strategies to enhance their stress tolerance are essential to their efficacy and commercial application. The current review provides an overview of the responses of antagonistic yeast species to various environmental stresses, the methods that can be used to improve stress tolerance and efficacy, and the related mechanisms associated with improved stress tolerance.
Yeast β-1,6-Glucan Is a Primary Target for the Saccharomyces cerevisiae K2 Toxin
Authors: Lukša Juliana , Podoliankaitė Monika , Vepštaitė Iglė , Strazdaitė-Žielienė Živilė , Urbonavičius Jaunius , Servienė Elena 
Published: February 2015

ABSTRACT

Certain
Saccharomyces cerevisiae
strains secrete different killer proteins of double-stranded-RNA origin. These proteins confer a growth advantage to their host by increasing its survival. K2 toxin affects the target cell by binding to the cell surface, disrupting the plasma membrane integrity, and inducing ion leakage. In this study, we determined that K2 toxin saturates the yeast cell surface receptors in 10 min. The apparent amount of K2 toxin, bound to a single cell of wild type yeast under saturating conditions, was estimated to be 435 to 460 molecules. It was found that an increased level of β-1,6-glucan directly correlates with the number of toxin molecules bound, thereby impacting the morphology and determining the fate of the yeast cell. We observed that the binding of K2 toxin to the yeast surface receptors proceeds in a similar manner as in case of the related K1 killer protein. It was demonstrated that the externally supplied pustulan, a poly-β-1,6-glucan, but not the glucans bearing other linkage types (such as laminarin, chitin, and pullulan) efficiently inhibits the K2 toxin killing activity. In addition, the analysis of toxin binding to the intact cells and spheroplasts confirmed that majority of K2 protein molecules attach to the β-1,6-glucan, rather than the plasma membrane-localized receptors. Taken together, our results reveal that β-1,6-glucan is a primary target of K2 toxin and is important for the execution of its killing property.
Crucial and Diverse Role of the Interleukin-33/ST2 Axis in Infectious Diseases
Authors: Rostan Octavie , Arshad Muhammad Imran , Piquet-Pellorce Claire , Robert-Gangneux Florence , Gangneux Jean-Pierre , Samson Michel 
Published: February 2015

ABSTRACT
Interleukin-33 (IL-33) has now emerged as a cytokine with diverse and pleiotropic functions in various infectious and inflammatory diseases. IL-33 is expressed by epithelial cells, endothelial cells, fibroblasts, and hepatocytes. The target cells of IL-33 are Th2 cells, basophils, dendritic cells, mast cells, macrophages, NKT cells, and nuocytes, newly discovered natural helper cells/innate lymphoid cells bearing the ST2 receptor. IL-33 has dual functions, both as a traditional cytokine and as a nuclear factor that regulates gene transcription. IL-33 functions as an “alarmin” released following cell death, as a biomarker, and as a vaccine adjuvant, with proinflammatory and protective effects during various infections. The exacerbated or protective role of the IL-33/ST2 axis during different infections is dependent upon the organ involved, type of infectious agent, whether the infection is acute or chronic, the invasiveness of the infectious agent, the host immune compartment, and cellular and cytokine microenvironments. In this review, we focus on recent advances in the understanding of the role of the IL-33/ST2 axis in various viral, bacterial, fungal, helminth, and protozoal infectious diseases gained from animal models and studies in human patients. The functional role of IL-33 and ST2 during experimentally induced infections has been summarized by accumulating the data for IL-33- and ST2-deficient mice or for mice exogenously administered IL-33. In summary, exploring the crucial and diverse roles of the IL-33/ST2 axis during infections may help in the development of therapeutic interventions for a wide range of infectious diseases.
Ixodes ricinus Salivary Serpin IRS-2 Affects Th17 Differentiation via Inhibition of the Interleukin-6/STAT-3 Signaling Pathway
Authors: Páleníková Jana , Lieskovská Jaroslava , Langhansová Helena , Kotsyfakis Michalis , Chmelař Jindřich , Kopecký Jan 
Published: February 2015

ABSTRACTTh17 cells constitute a subset of CD4+T lymphocytes that play a crucial role in protection against extracellular bacteria and fungi. They are also associated with tissue injury in autoimmune and inflammatory diseases. Here, we report that serpin from the tickIxodes ricinus, IRS-2, inhibits Th17 differentiation by impairment of the interleukin-6 (IL-6)/STAT-3 signaling pathway. Following activation, mature dendritic cells produce an array of cytokines, including the pleiotropic cytokine IL-6, which triggers the IL-6 signaling pathway. The major transcription factor activated by IL-6 is STAT-3. We show that IRS-2 selectively inhibits production of IL-6 in dendritic cells stimulated withBorreliaspirochetes, which leads to attenuated STAT-3 phosphorylation and finally to impaired Th17 differentiation. The results presented extend the knowledge about the effect of tick salivary serpins on innate immunity cells and their function in driving adaptive immune responses.
Differential Immunodetection of Toxin B from Highly Virulent Clostridium difficile BI/NAP-1/027
Authors: Pollock Nira R. , Song Linan , Zhao Mingwei , Duffy David C. , Chen Xinhua , Sambol Susan P. , Gerding Dale N. , Kelly Ciarán P. 
Published: February 2015

ABSTRACT

We developed a simple immunoassay capable of differentially detecting toxin B from highly virulent strains of
Clostridium difficile
(BI/NAP-1/027) in stool. This assay can simultaneously confirm the presence of
in vivo
toxin production and provide strain-related information relevant to infection control epidemiology and disease prognosis.
Gammaherpesvirus Tegument Protein ORF33 Is Associated with Intranuclear Capsids at an Early Stage of the Tegumentation Process
Authors: Shen Sheng , Jia Xing , Guo Haitao , Deng Hongyu 
Published: February 2015

ABSTRACT

Herpesvirus nascent capsids, after assembly in the nucleus, must acquire a variety of tegument proteins during maturation. However, little is known about the identity of the tegument proteins that are associated with capsids in the nucleus or the molecular mechanisms involved in the nuclear egress of capsids into the cytoplasm, especially for the two human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), due to a lack of efficient lytic replication systems. Murine gammaherpesvirus 68 (MHV-68) is genetically related to human gammaherpesviruses and serves as an excellent model to study the
de novo
lytic replication of gammaherpesviruses. We have previously shown that open reading frame 33 (ORF33) of MHV-68 is a tegument protein of mature virions and is essential for virion assembly and egress. However, it remains unclear how ORF33 is incorporated into virions. In this study, we first show that the endogenous ORF33 protein colocalizes with capsid proteins at discrete areas in the nucleus during viral infection. Cosedimentation analysis as well as an immunoprecipitation assay demonstrated that ORF33 is associated with both nuclear and cytoplasmic capsids. An immunogold labeling experiment using an anti-ORF33 monoclonal antibody revealed that ORF33-rich areas in the nucleus are surrounded by immature capsids. Moreover, ORF33 is associated with nucleocapsids prior to primary envelopment as well as with mature virions in the cytoplasm. Finally, we show that ORF33 interacts with two capsid proteins, suggesting that nucleocapsids may interact with ORF33 in a direct manner. In summary, we identified ORF33 to be a tegument protein that is associated with intranuclear capsids prior to primary envelopment, likely through interacting with capsid proteins in a direct manner.

IMPORTANCE
Morphogenesis is an essential step in virus propagation that leads to the generation of progeny virions. For herpesviruses, this is a complicated process that starts in the nucleus. Although the process of capsid assembly and genome packaging is relatively well understood, how capsids acquire tegument (the layer between the capsid and the envelope in a herpesvirus virion) and whether the initial tegumentation process takes place in the nucleus remain unclear. We previously showed that ORF33 of MHV-68 is a tegument protein and functions in both the nuclear egress of capsids and final virion maturation in the cytoplasm. In the present study, we show that ORF33 is associated with intranuclear capsids prior to primary envelopment and identify novel interactions between ORF33 and two capsid proteins. Our work provides new insights into the association between tegument proteins and nucleocapsids at an early stage of the virion maturation process for herpesviruses.
A Novel Endogenous Betaretrovirus in the Common Vampire Bat (Desmodus rotundus) Suggests Multiple Independent Infection and Cross-Species Transmission Events
Authors: Escalera-Zamudio Marina , Mendoza M. Lisandra Zepeda , Heeger Felix , Loza-Rubio Elizabeth , Rojas-Anaya Edith , Méndez-Ojeda Maria L. , Taboada Blanca , Mazzoni Camila J. , Arias Carlos F. , Greenwood Alex D. 
Published: February 2015

ABSTRACT

The
Desmodus rotundus
endogenous betaretrovirus (DrERV) is fixed in the vampire bat
D. rotundus
population and in other phyllostomid bats but is not present in all species from this family. DrERV is not phylogenetically related to Old World bat betaretroviruses but to betaretroviruses from rodents and New World primates, suggesting recent cross-species transmission. A recent integration age estimation of the provirus in some taxa indicates that an exogenous counterpart might have been in recent circulation.
Infection History Determines the Differentiation State of Human CD8
+
T Cells
Authors: van Aalderen Michiel C. , Remmerswaal Ester B. M. , Verstegen Niels J. M. , Hombrink Pleun , ten Brinke Anja , Pircher Hanspeter , Kootstra Neeltje A. , ten Berge Ineke J. M. , van Lier René A. W. 
Published: February 2015

ABSTRACT

After the resolution of the acute phase of infection, otherwise quiescent antigen-experienced CD8
+
T cells confer rapid protection upon reinfection with viral pathogens or, in the case of persistent viruses, help to maintain control of the infection. Depending on the type of virus, antigen-specific CD8
+
T cells have distinct traits, ranging from typical memory cell properties in the case of rapidly cleared viruses to immediate effector functions for persistent viruses. We here show that both the differentiation stage, defined by the expression of cell surface markers, such as CD45RA, CCR7, CD28, and CD27, and distinct expression levels of T-bet and eomesodermin (Eomes) predict the functional profile of antigen-experienced CD8
+
T cells. Furthermore, virus-specific CD8
+
T cells targeting different respiratory syncytial virus-, influenza A virus-, Epstein-Barr virus (EBV)-, human cytomegalovirus (hCMV)-, and HIV-1-specific epitopes adopt distinct T-bet and Eomes expression patterns that appear to be installed early during the primary response. Importantly, the associations between surface phenotype, T-bet/Eomes expression levels, and the expression of markers that predict CD8
+
T-cell function change according to viral infection history, particularly against the background of HIV-1 and, to lesser extent, of human cytomegalovirus and/or Epstein-Barr virus infection. Thus, the functionality of human antigen-experienced CD8
+
T cells follows at least two dimensions, one outlined by the surface phenotype and another by the T-bet/Eomes expression levels, which are determined by previous or persistent viral challenges.

IMPORTANCE
Functional human CD8
+
T-cell subsets have been defined using surface markers like CD45RA, CCR7, CD28, and CD27. However, the induction of function-defining traits, like granzyme B expression, is controlled by transcription factors like T-bet and Eomes. Here, we describe how T-bet and Eomes levels distinctly relate to the expression of molecules predictive for CD8
+
T-cell function in a surface phenotype-independent manner. Importantly, we found that central memory and effector memory CD8
+
T-cell subsets differentially express T-bet, Eomes, and molecules predictive for function according to viral infection history, particularly so in the context of HIV-1 infection and, to lesser extent, of latent EBV- and/or hCMV-infected, otherwise healthy adults. Finally, we show that the distinct phenotypes and T-bet/Eomes levels of different virus-specific CD8
+
T-cell populations are imprinted early during the acute phase of primary infection
in vivo
. These findings broaden our understanding of CD8
+
T-cell differentiation.
Cellular Transformation of Mouse Embryo Fibroblasts in the Absence of Activator E2Fs
Authors: Gupta Tushar , Sáenz Robles Maria Teresa , Pipas James M. 
Published: February 2015

ABSTRACT
The E2F family of transcription factors, broadly divided into activator and repressor E2Fs, regulates cell cycle genes. Current models indicate that activator E2Fs are necessary for cell cycle progression and tumorigenesis and are also required to mediate transformation induced by DNA tumor viruses. E2Fs are negatively regulated by the retinoblastoma (RB) family of tumor suppressor proteins, and virus-encoded oncogenes disrupt the RB-E2F repressor complexes. This results in the release of activator E2Fs and induction of E2F-dependent genes. In agreement, expression of large tumor T antigens (TAg) encoded by polyomaviruses in mammalian cells results in increased transcriptional levels of E2F target genes. In addition, tumorigenesis induced by transgenic expression of simian virus 40 (SV40) TAg in choroid plexus or intestinal villi requires at least one activator E2F. In contrast, we show that SV40 TAg-induced transformation in mouse embryonic fibroblasts is independent of activator E2Fs. This work, coupled with recent studies showing that proliferation in stem and progenitor cells is independent of activator E2Fs, suggests the presence of parallel pathways governing cell proliferation and tumorigenesis.

IMPORTANCE
The RB-E2F pathway is altered in many cancers and is also targeted by DNA tumor viruses. Viral oncoprotein action on RBs results in the release of activator E2Fs and upregulation of E2F target genes; thus, activator E2Fs are considered essential for normal and tumorigenic cell proliferation. However, we have observed that SV40 large T antigen can induce cell proliferation and transformation in the absence of activator E2Fs. Our results also suggest that TAg action on pRBs regulates both E2F-dependent and -independent pathways that govern proliferation. Thus, specific cell proliferation pathways affected by RB alterations in cancer may be a factor in tumor behavior and response to therapy.
Novel Pseudotaxis Mechanisms Improve Migration of Straight-Swimming Bacterial Mutants Through a Porous Environment
Authors: Mohari Bitan , Licata Nicholas A. , Kysela David T. , Merritt Peter M. , Mukhopadhay Suchetana , Brun Yves V. , Setayeshgar Sima , Fuqua Clay 
Published: February 2015

ABSTRACT

Bacterial locomotion driven by flagella is given directionality by the chemotaxis signal transduction network. In the classic plate assays of migration in porous motility agar, efficient motility is compromised in chemotaxis mutants of diverse bacteria. Nonchemotactic mutants become trapped within the agar matrix. Suppressor mutations that prevent this entanglement but do not restore chemotaxis, a phenomenon designated pseudotaxis, were first reported to arise for
Escherichia coli
. In this study, novel mechanisms of pseudotaxis have been identified for the plant-pathogenic alphaproteobacterium
Agrobacterium tumefaciens
. Mutants with chemotaxis mutation suppressor (cms) mutations that impart enhanced migration in motility agar compared to that of their straight-swimming, nonchemotactic parent were isolated. We find that pseudotaxis in A. tumefaciens occurs most commonly via mutations in the D1 domain of the flagellar hook protein, FlgE, but it can also be found less frequently to be due to mutations in the hook length regulator, FliK, or in the motor protein, MotA. Single-cell-tracking studies of cms mutants in bulk medium clearly reveal frequent changes in the direction of swimming, similar to the swimming of strains that are proficient for chemotaxis, but independent of a sensory mechanism. Our results suggest that the tumbling process can be tuned through mutation and evolution to optimize migration through complex, porous environments.

IMPORTANCE
Chemotaxis sensory networks control direct bacterial motility by modulating flagellar rotary motion, alternating cellular movement between runs and tumbles. The straight-swimming phenotype of chemotaxis-deficient cells yields nonexpanding colonies in motility agar. Enhanced, chemotaxis-independent spreading, dubbed pseudotaxis, has been observed in
Escherichia coli
mutants. We have identified novel pseudotaxis mutations in
Agrobacterium tumefaciens
that alter the flagellar hook structure or motor, leading to randomly occurring reorientations observed in single-cell tracking studies in bulk medium. These directional changes allow the cells to migrate more efficiently than the parent strain through the agar matrix, independently of the chemotaxis process. These findings reveal that tumbling can be tuned for effective navigation in complex porous environments, analogous to the natural habitats for many bacteria, and provide evidence for the strong selective pressure exerted by the external environment on the basal pattern of motility, even in the absence of chemotaxis.
Toxoplasma gondii Superinfection and Virulence during Secondary Infection Correlate with the ExactROP5/ROP18Allelic Combination
Authors: Jensen Kirk D. C. , Camejo Ana , Melo Mariane B. , Cordeiro Cynthia , Julien Lindsay , Grotenbreg Gijsbert M. , Frickel Eva-Maria , Ploegh Hidde L. , Young Lucy , Saeij Jeroen P. J. 
Published: February 2015

ABSTRACTThe intracellular parasiteToxoplasma gondiiinfects a wide variety of vertebrate species globally. Infection in most hosts causes a lifelong chronic infection and generates immunological memory responses that protect the host against new infections. In regions where the organism is endemic, multiple exposures toT. gondiilikely occur with great frequency, yet little is known about the interaction between a chronically infected host and the parasite strains from these areas. A widely used model to explore secondary infection entails challenge of chronically infected or vaccinated mice with the highly virulent type I RH strain. Here, we show that although vaccinated or chronically infected C57BL/6 mice are protected against the type I RH strain, they are not protected against challenge with most strains prevalent in South America or another type I strain, GT1. Genetic and genomic analyses implicated the parasite-secreted rhoptry effectors ROP5 and ROP18, which antagonize the host's gamma interferon-induced immunity-regulated GTPases (IRGs), as primary requirements for virulence during secondary infection. ROP5 and ROP18 promoted parasite superinfection in the brains of challenged survivors. We hypothesize that superinfection may be an important mechanism to generateT. gondiistrain diversity, simply because two parasite strains would be present in a single meal consumed by the feline definitive host. Superinfection may drive the genetic diversity of Toxoplasma strains in South America, where most isolates are IRG resistant, compared to North America, where most strains are IRG susceptible and are derived from a few clonal lineages. In summary, ROP5 and ROP18 promote Toxoplasma virulence during reinfection.IMPORTANCEToxoplasma gondiiis a widespread parasite of warm-blooded animals and currently infects one-third of the human population. A long-standing assumption in the field is that prior exposure to this parasite protects the host from subsequent reexposure, due to the generation of protective immunological memory. However, this assumption is based on clinical data and mouse models that analyze infections with strains common to Europe infections with strains common to Europe and North America. In contrast, we found that the majority of strains sampled from around the world, in particular those from South America, were able to kill or reinfect the brains of hosts previously exposed toT. gondii. TheT. gondiivirulence factors ROP5 and ROP18, which inhibit key host effectors that mediate parasite killing, were required for these phenotypes. We speculate that these results underpin clinical observations that pregnant women previously exposed to Toxoplasma can develop congenital infection upon reexposure to South American strains.