scholarly journals The bunyavirus nonstructural protein NSs suppresses plant immunity to facilitate its own transmission by improving vector insect performance

2018 ◽  
Author(s):  
Xiujuan Wu ◽  
Shuang Xu ◽  
Pingzhi Zhao ◽  
Xiangmei Yao ◽  
Yanwei Sun ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Plant Pathogens ◽  
Molecular Mechanisms ◽  
Nonstructural Protein ◽  
Pathogen Transmission ◽  
Terpene Synthase ◽  
Silencing Suppressor ◽  
Suppressor Activity ◽  
Arthropod Vectors ◽  
Vector Behavior

AbstractPandemics of vector-borne human and plant pathogens often rely on the behaviors of their arthropod vectors. Arboviruses, including many bunyaviruses, manipulate vector behavior to accelerate their own transmission to vertebrates, birds, insects, and plants. However, the molecular mechanism underlying this manipulation remains elusive. Here, we report that the non-structural protein NSs of orthotospovirus (order Bunyavirales, family Tospoviridae), is a key viral factor that indirectly modifies vector preference and increases vector performance. NSs suppresses the biosynthesis of volatile monoterpenes, which serve as repellents of the vector Western flower thrips (WFT, Frankliniella occidentalis) instead of using its known silencing suppressor activity. NSs directly interacts with and relocalizes the jasmonate (JA) signaling master regulator MYC2 and its two close homologs, MYC3 and MYC4, to disable JA-mediated activation of terpene synthase genes. The dysfunction of the MYCs subsequently attenuates host defenses, increases the attraction of thrips, and improves thrips fitness. These findings elucidate the molecular mechanism through which a bunyavirus manipulates vector behaviors and therefore facilitate disease transmission. Our results provide important insights into the molecular mechanisms by which tospoviruses NSs counteracts host immunity for pathogen transmission.Author summaryMost bunyaviruses are transmitted by insect vectors, and some of them can modify the behaviors of their arthropod vectors to increase transmission to mammals, birds, and plants. NSs is a non-structural bunyavirus protein with multiple functions that acts as an avirulence determinant and silencing suppressor. In this study, we identified a new function of NSs as a manipulator of vector behavior, independent of its silencing suppressor activity. NSs manipulates jasmonate-mediated immunity against thrips by directly interacting with several homologs of MYC transcription factors, the core regulators of the jasmonate-signaling pathway. This hijacking by NSs enhances thrips preference and performance. Many human- and animal-infecting members of the Bunyaviridales also encode NSs and could manipulate vector behavior to accelerate their own transmission. Therefore, our data support the hypothesis that the NSs protein may play conserved roles among various members of the Bunyaviridales in the modification of vector feeding behavior that evolved as a mechanism to enhance virus transmission.

Cellular and molecular mechanisms of statins: an update on pleiotropic effects

2015 ◽  
Vol 129 (2) ◽  
pp. 93-105 ◽  
Author(s):  
Mamoru Satoh ◽  
Yuji Takahashi ◽  
Tsuyoshi Tabuchi ◽  
Yoshitaka Minami ◽  
Makiko Tamada ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Chronic Inflammation ◽  
Molecular Mechanism ◽  
Coronary Atherosclerosis ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Plaque Instability ◽  
Beneficial Effects ◽  
Reductase Inhibitors ◽  
Artery Disease

Coronary artery disease (CAD) is the leading cause of death worldwide. The efficacy and safety of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) in primary and secondary prevention of CAD are confirmed in several large studies. It is well known that statins have some pleiotropic, anti-atherosclerotic effects. We review the molecular mechanisms underlying the beneficial effects of statins revealed in recently published studies. Endothelial cell injury is regarded as the classic stimulus for the development of atherosclerotic lesions. In addition, the inflammatory process plays an important role in the aetiology of atherosclerosis. In particular, chronic inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. Our previous reports and others have demonstrated beneficial effects of statins on endothelial dysfunction and chronic inflammation in CAD. A better understanding of the molecular mechanism underlying the effectiveness of statins against atherosclerosis may provide a novel therapeutic agent for the treatment of coronary atherosclerosis. The present review summarizes the cellular and molecular mechanism of statins against coronary atherosclerosis.

scholarly journals Higher Variability in Fungi Compared to Bacteria in the Foraging Honey Bee Gut

2020 ◽  
Author(s):  
Leslie E. Decker ◽  
Priscilla A. San Juan ◽  
Magdalena L. Warren ◽  
Cory E. Duckworth ◽  
Cheng Gao ◽  
...  
Keyword(s):  
Species Composition ◽  
Microbial Communities ◽  
Honey Bee ◽  
Honey Bees ◽  
Plant Pathogens ◽  
Distribution Patterns ◽  
Model System ◽  
Pathogen Transmission ◽  
Host Health ◽  
Gut Symbionts

AbstractMicrobial communities in the honey bee gut have emerged as a model system to understand the effects of host-associated microbes on animals and plants. The specific distribution patterns of bacterial associates among honey bee gut regions remains a key finding within the field. The mid- and hindgut of foraging bees house a deterministic set of core species that affect host health. In contrast, the crop, or honey stomach, contains a more diverse set of bacteria that is highly variable in composition among individual bees. Whether this contrast between the two gut regions also applies to fungi, another major group of gut-associated microbes, remains unclear despite their potential influence on host health. In honey bees caught foraging at four sites across the San Francisco Peninsula, we found that fungi were much less distinct in species composition between the crop and the mid- and hindgut than bacteria. Unlike bacteria, fungi were highly variable in composition throughout the gut, and much of this variation was attributable to bee collection site. These patterns suggest that the fungi may be passengers rather than functionally significant gut symbionts. However, many of the fungi we found in the bees have been recognized as plant pathogens. Assuming that some fungi remain viable after passage through the gut, the distribution patterns we report here point to the potential importance of honey bees as vectors of fungal pathogens and suggest a more prominent role of honey bees in plant pathogen transmission than generally thought.Importance (Nontechnical explanation of why the work was undertaken)Along with bacteria, fungi make up a significant portion of animal- and plant-associated microbial communities. However, we have only begun to describe these fungi, much less examine their effects on most animals and plants. The honey bee, Apis mellifera, has emerged as a model system for studying host-associated microbes. Honey bees contain well-characterized bacteria specialized to inhabit different regions of the gut. Fungi also exist in the honey bee gut, but their composition and function remain largely undescribed. Here we show that, unlike bacteria, fungi vary substantially in species composition throughout the honey bee gut, contingent on where the bees are sampled. This observation suggests that fungi may be transient passengers and therefore unimportant as gut symbionts. However, our findings also indicate that honey bees could be major vectors of infectious plant diseases as many of the fungi we found in the honey bee gut are recognized as plant pathogens.

scholarly journals Polar relaxation by dynein-mediated removal of cortical myosin II

2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Bernardo Chapa-y-Lazo ◽  
Motonari Hamanaka ◽  
Alexander Wray ◽  
Mohan K. Balasubramanian ◽  
Masanori Mishima
Keyword(s):  
Recent Work ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Myosin Ii ◽  
Cell Cortex ◽  
Cleavage Furrow ◽  
Contractile Ring ◽  
C Elegans ◽  
Polar Cell

Nearly six decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction. While this mechanism has remained controversial, recent work has provided evidence for polar relaxation by astral microtubules, although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar relaxation is achieved through dynein-mediated removal of myosin II from the polar cortexes. Mutants that position centrosomes closer to the polar cortex accelerated furrow induction, whereas suppression of dynein activity delayed furrowing. We show that dynein-mediated removal of myosin II from the polar cortexes triggers a bidirectional cortical flow toward the cell equator, which induces the assembly of the actomyosin contractile ring. These results provide a molecular mechanism for the aster-dependent polar relaxation, which works in parallel with equatorial stimulation to promote robust cytokinesis.

scholarly journals Beneficial Impact and Molecular Mechanism of Bacillus Coagulans on Piglets Intestine

2018 ◽  
Author(s):  
Tao Wu ◽  
Yang Lv ◽  
Xueni Li ◽  
Lin Zhang ◽  
Yutao Shi ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Bacillus Coagulans ◽  
Basal Diet ◽  
Control Group ◽  
Villus Height ◽  
Intestinal Integrity ◽  
Beneficial Impact ◽  
Related Proteins

This research was to investigate beneficial impact and molecular mechanism of B. coagulans on piglets intestine. Twenty-four 21 days old weaned piglets were allotted to three treatments: control group (basal diet), B6 group (basal diet + 2×106 CFU/g B. coagulans), B7 group (basal diet + 2×107 CFU/g B. coagulans). The results showed that compared with control group, B6 and B7 group significantly decreased diarrhea rate and the concent of CHOL, GGT and DAO in plasma; decreased villus height and increase crypt depth in jejunum and ileum; increased the activities of SOD and CAT and decreased the concent of MDA and H2O2 in intestine. These data suggested that supplementing B. coagulans had beneficial impacts on promoting nutrients metabolism, maintaining intestinal integrity and alleviating oxidative stress and diarrhea. Futher research of molecular mechanisms showed that, these beneficial impacts were regulated by changing expression levels of related proteins (including HSP70, Caspase-3, Bax, Villin and Occludin), and genes (including RPL4, IFN-α, IFN-β, IFN-γ, MX1, MX2, OAS1, IL-1β, IL-4, CXCL-9, CCL-2, AQP3, SGLT-1, LPL, INSR and b0,+AT), and altering community composition of gut microbiota (particularly family Clostridiaceae, Enterobacteriaceae, and Veillonellaceae and genus Prevotella, Turicibacter, and Lactobacillus).

scholarly journals Molecular basis for two stereoselective Diels-Alderases that produce decalin skeletons

2021 ◽  
Author(s):  
Keisuke Fujiyama ◽  
Naoki Kato ◽  
Suyong Re ◽  
Kiyomi Kinugasa ◽  
Kohei Watanabe ◽  
...  
Keyword(s):  
Natural Products ◽  
Crystal Structures ◽  
Molecular Mechanism ◽  
Density Functional ◽  
Molecular Mechanisms ◽  
Site Directed Mutagenesis ◽  
Bioactive Molecules ◽  
Docking Simulations ◽  
Primary And Secondary Metabolites ◽  
Binding Models

SummaryMolecular chirality, discovered by Louis Pasteur in the middle of the 19th century1, is found in most primary and secondary metabolites. Particularly, the so-called natural products are rich in chiral centres2. The stereochemistry of natural products is strictly recognized in living organisms, and is thus closely related to their biological functions. The Diels–Alder (DA) reaction, which forms a six-membered ring with up to four chiral centres, is a fundamental practical reaction for C–C bond formation in synthetic chemistry3. Nature has also adopted this reaction to elaborate the complex structures of natural products using enzymes derived from various progenitor proteins4-7. Although enzymes catalysing the DA reaction, Diels–Alderases (DAases), have attracted increasing attention, little is known about the molecular mechanism by which they control the stereochemistry and perform catalysis. Here, we solved the X-ray crystal structures of a pair of decalin synthases, Fsa2 and Phm7, that catalyse intramolecular DA reactions to form enantiomeric decalin scaffolds during biosynthesis of the HIV-1 integrase inhibitor equisetin and its stereochemical opposite, phomasetin8,9. Based on the crystal structures, docking simulations followed by all-atom molecular dynamics simulations provided dynamic binding models demonstrating the folding of linear polyenoyl tetramic acid substrates in the binding pocket of these enzymes, explaining the stereoselectivity in the construction of decalin scaffolds. Site-directed mutagenesis studies verified the binding models and, in combination with density functional theory calculations, clarified how hydrophilic amino acid residues in the Phm7 pocket regulate and catalyse the stereoselective DA reaction. This study highlights the distinct molecular mechanisms of the enzymatic DA reaction and its stereoselectivity experimentally and computationally. We anticipate that clarified molecular mechanism herein provides not only the basic understanding how these important enzymes work but also the guiding principle to create artificial enzymes that produce designer bioactive molecules.

Transcriptomic response ofRalstonia solanacearumto antimicrobialPseudomonas fluorescensSN15-2 metabolites

2018 ◽  
Vol 64 (11) ◽  
pp. 816-825 ◽  
Author(s):  
Haibo Lou ◽  
Xiaobing Wang ◽  
Jun Chen ◽  
Bozhi Wang ◽  
Wei Wang
Keyword(s):  
Oxidative Stress ◽  
Plant Pathogens ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Iron Absorption ◽  
Fermentation Broth ◽  
Transcriptomic Response ◽  
Transmission Electron ◽  
Antimicrobial Metabolites ◽  
Tomato Wilt

To develop efficient biocontrol agents, it is essential to investigate the response of soil-borne plant pathogens to such agents. For example, the response of Ralstonia solanacearum, the tomato wilt pathogen, to antimicrobial metabolites of Pseudomonas fluorescens is unknown. Thus, we assessed the effects of P. fluorescens SN15-2 fermentation broth on R. solanacearum by transmission electron microscopy and transcriptome technology. RNA sequencing identified 109 and 155 genes that are significantly upregulated and downregulated, respectively, in response to P. fluorescens metabolites, many of which are associated with the cell membrane and cell wall, and with nucleotide acid metabolism, iron absorption, and response to oxidative stress. This study highlights the effectiveness of P. fluorescens metabolites against the tomato wilt pathogen and helps clarify the underlying molecular mechanisms.

scholarly journals Tracing the Lineage of Two Traits Associated with the Coat Protein of the Tombusviridae: Silencing Suppression and HR Elicitation in Nicotiana Species

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 588 ◽  
Author(s):  
Mustafa Adhab ◽  
Carlos Angel ◽  
Andres Rodriguez ◽  
Mohammad Fereidouni ◽  
Lóránt Király ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Structural Changes ◽  
Coat Proteins ◽  
Silencing Suppressor ◽  
Suppressor Activity ◽  
Nicotiana Species ◽  
Pathogen Effector ◽  
The Family ◽  
Silencing Suppression ◽  
Insight Into

In this paper we have characterized the lineage of two traits associated with the coat proteins (CPs) of the tombusvirids: Silencing suppression and HR elicitation in Nicotiana species. We considered that the tombusvirid CPs might collectively be considered an effector, with the CP of each CP-encoding species comprising a structural variant within the family. Thus, a phylogenetic analysis of the CP could provide insight into the evolution of a pathogen effector. The phylogeny of the CP of tombusvirids indicated that CP representatives of the family could be divided into four clades. In two separate clades the CP triggered a hypersensitive response (HR) in Nicotiana species of section Alatae but did not have silencing suppressor activity. In a third clade the CP had a silencing suppressor activity but did not have the capacity to trigger HR in Nicotiana species. In the fourth clade, the CP did not carry either function. Our analysis illustrates how structural changes that likely occurred in the CP effector of progenitors of the current genera led to either silencing suppressor activity, HR elicitation in select Nicotiana species, or neither trait.

scholarly journals Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Interleukin-17 Production via Activation of the IRAK1-PI3K-p38MAPK-C/EBPβ/CREB Pathways

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Honglei Wang ◽  
Li Du ◽  
Fang Liu ◽  
Zeyu Wei ◽  
Li Gao ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Molecular Mechanisms ◽  
Nonstructural Protein ◽  
Severe Pneumonia ◽  
Pi3k Inhibitor ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Binding Motif ◽  
Interleukin 17 ◽  
Highly Pathogenic

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) is widely prevalent in pigs, resulting in significant economic losses worldwide. A compelling impact of PRRSV infection is severe pneumonia. In the present study, we found that interleukin-17 (IL-17) was upregulated by PRRSV infection. Subsequently, we demonstrated that PI3K and p38MAPK signaling pathways were essential for PRRSV-induced IL-17 production as addition of phosphatidylinositol 3-kinase (PI3K) and p38MAPK inhibitors dramatically reduced IL-17 production. Furthermore, we show here that deleting the C/EBPβ and CREB binding motif in porcine IL-17 promoter abrogated its activation and that knockdown of C/EBPβ and CREB remarkably impaired PRRSV-induced IL-17 production, suggesting that IL-17 expression was dependent on C/EBPβ and CREB. More specifically, we demonstrate that PRRSV nonstructural protein 11 (nsp11) induced IL-17 production, which was also dependent on PI3K-p38MAPK-C/EBPβ/CREB pathways. We then show that Ser74 and Phe76 amino acids were essential for nsp11 to induce IL-17 production and viral rescue. In addition, IRAK1 was required for nsp11 to activate PI3K and enhance IL-17 expression by interacting with each other. Importantly, we demonstrate that PI3K inhibitor significantly suppressed IL-17 production and lung inflammation caused by HP-PRRSV in vivo, implicating that higher IL-17 level induced by HP-PRRSV might be associated with severe lung inflammation. These findings provide new insights onto the molecular mechanisms of the PRRSV-induced IL-17 production and help us further understand the pathogenesis of PRRSV infection. IMPORTANCE Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) associated with severe pneumonia has been one of the most important viral pathogens in pigs. IL-17 is a proinflammatory cytokine that might be associated with the strong inflammation caused by PRRSV. Therefore, we sought to determine whether PRRSV infection affects IL-17 expression, and if so, determine this might partially explain the underlying mechanisms for the strong inflammation in HP-PRRSV-infected pigs, especially in lungs. Here, we show that PRRSV significantly induced IL-17 expression, and we subsequently dissected the molecular mechanisms about how PRRSV regulated IL-17 production. Furthermore, we show that Ser74 and Phe76 in nsp11 were indispensable for IL-17 production and viral replication. Importantly, we demonstrated that PI3K inhibitor impaired IL-17 production and alleviated lung inflammation caused by HP-PRRSV infection. Our findings will help us for a better understanding of PRRSV pathogenesis.

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