Infectious diseases caused by human immunodeficiency virus (HIV) and other highly pathogenic enveloped viruses, have threatened the global public health. Most antiviral drugs act as passive defenders to inhibit viral replication inside the cell, while a few of them function as gate keepers to combat viruses outside the cell, including fusion inhibitors, e.g., enfuvirtide, and receptor antagonists, e.g., maraviroc, as well as virus inactivators (including attachment inhibitors). Different from fusion inhibitors and receptor antagonists that must act in the presence of target cells, virus inactivators can actively inactivate cell-free virions in the blood, through interaction with one or more sites in the envelope glycoproteins (Envs) on virions. Notably, a number of protein- and peptide-based virus inactivators (PPVIs) under development are expected to have a better utilization rate than the current antiviral drugs and be safer for in vivo human application than the chemical-based virus inactivators. Here we have highlighted recent progress in developing PPVIs against several important enveloped viruses, including HIV, influenza virus, Zika virus (ZIKV), dengue virus (DENV), and herpes simplex virus (HSV), and the potential use of PPVIs for urgent treatment of infection by newly emerging or re-emerging viruses.Since intracellular survival of all chlamydiae depends on the manipulation of the host cell through type III secreted effector proteins, their characterization is crucial for the understanding of chlamydial pathogenesis. We functionally characterized the putative type III secreted Chlamydia abortus protein CAB063, describe its intracellular localization and identified pro- and eukaryotic binding partners. Based on an experimental infection model and plasmid transfections, we investigated the subcellular localization of CAB063 by immunofluorescence microscopy, immunoelectron microscopy, and Western blot analysis. Pro- and eukaryotic targets were identified by co-immunofluorescence, co-immunoprecipitation, and mass spectrometry. Transmission electron microscopy and flow cytometry were used for morphological and functional investigations on host cell apoptosis. CAB063 localized in the nuclear membrane of the host cell nucleus and we identified the chaperone HSP70 and lamin A/C as pro- and eukaryotic targets, respectively. CAB063-dependent morphological alterations of the host cell nucleus correlated with increased apoptosis rates of infected and CAB063-transfected cells. We provide evidence that CAB063 is a chaperone-folded type III secreted C. abortus virulence factor that targets lamin thereby altering the host cell nuclear membrane structure. This process may be responsible for an increased apoptosis rate at the end of the chlamydial developmental cycle, at which CAB063 is physiologically expressed.Healthy soil microbiomes are crucial for achieving high productivity in combination with crop quality, but our understanding of microbial diversity is still limited. In a large-scale study including 116 composite samples from vineyards, orchards and other crops from all over Styria (south-east Austria), agricultural management as well as distinct soil parameters were identified as drivers of the indigenous microbial communities in agricultural soils. The analysis of the soil microbiota based on microbial profiling of prokaryotic 16S rRNA gene fragments and fungal ITS regions revealed high bacterial and fungal diversity within Styrian agricultural soils; 206,596 prokaryotic and 53,710 fungal OTUs. Vineyards revealed a significantly higher diversity and distinct composition of soil fungi over orchards and other agricultural soils, whereas the prokaryotic diversity was unaffected. Soil pH was identified as one of the most important edaphic modulators of microbial community structure in both, vineyard and orchardThese findings provide the basis to adapt soil management practices in the future in order to maintain a healthy microbiome in agricultural soils.[This corrects the article DOI 10.3389/fmicb.2019.03039.].Phytoplankton are major contributors to labile organic matter in the upper ocean. Diverse heterotrophic bacteria successively metabolize these labile compounds and drive elemental biogeochemical cycling. We investigated the bioavailability of Synechococcus-derived organic matter (SOM) by estuarine and coastal microbes during 180-day dark incubations. Variations in organic carbon, inorganic nutrients, fluorescent dissolved organic matter (FDOM), and total/active microbial communities were monitored. The entire incubations could be partitioned into three phases (labeled I, II, and III) based on the total organic carbon (TOC) consumption rates of 6.38-7.01, 0.53-0.64, and 0.10-0.13 μmol C L-1 day-1, respectively. This corresponded with accumulation processes of NH4 +, NO2 -, and NO3 -, respectively. One tryptophan-like (C1) and three humic-like (C2, C3, and C4) FDOM components were identified. The intensity variation of C1 followed bacterial growth activities, and C2, C3, and C4 displayed labile, semi-labile, and refractory DOM characteristics, respectively. Alphaproteobacteria, Gammaproteobacteria, Bacteroidetes, and Actinobacteria dominated the quickly consumed process of SOM (phase I) coupled with a substantial amount of NH4 + generation. https://www.selleckchem.com/products/kpt-9274.html Thaumarchaeota became an abundant population with the highest activities in phase II, especially in the free-living size-fraction, and these organisms could perform chemoautotroph processes through the ammonia oxidation. Microbial populations frequently found in the dark ocean, even the deep sea, became abundant during phase III, in which Nitrospinae/Nitrospirae obtained energy through nitrite oxidation. Our results shed light on the transformation of different biological availability of organic carbon by coastal microorganisms which coupled with the regeneration of different form of inorganic nitrogen.The negative effects of honey bee parasitic mites and deformed wing virus (DWV) on honey bee and colony health have been well characterized. However, the relationship between DWV and mites, particularly viral replication inside the mites, remains unclear. Furthermore, the physiological outcomes of honey bee immune responses stimulated by DWV and the mite to the host (honey bee) and perhaps the pathogen/parasite (DWV/mite) are not yet understood. To answer these questions, we studied the tripartite interactions between the honey bee, Tropilaelaps mercedesae, and DWV as the model. T. mercedesae functioned as a vector for DWV without supporting active viral replication. Thus, DWV negligibly affected mite fitness. Mite infestation induced mRNA expression of antimicrobial peptides (AMPs), Defensin-1 and Hymenoptaecin, which correlated with DWV copy number in honey bee pupae and mite feeding, respectively. Feeding T. mercedesae with fruit fly S2 cells heterologously expressing honey bee Hymenoptaecin significantly downregulated mite Vitellogenin expression, indicating that the honey bee AMP manipulates mite reproduction upon feeding on bee.
Infectious diseases caused by human immunodeficiency virus (HIV) and other highly pathogenic enveloped viruses, have threatened the global public health. Most antiviral drugs act as passive defenders to inhibit viral replication inside the cell, while a few of them function as gate keepers to combat viruses outside the cell, including fusion inhibitors, e.g., enfuvirtide, and receptor antagonists, e.g., maraviroc, as well as virus inactivators (including attachment inhibitors). Different from fusion inhibitors and receptor antagonists that must act in the presence of target cells, virus inactivators can actively inactivate cell-free virions in the blood, through interaction with one or more sites in the envelope glycoproteins (Envs) on virions. Notably, a number of protein- and peptide-based virus inactivators (PPVIs) under development are expected to have a better utilization rate than the current antiviral drugs and be safer for in vivo human application than the chemical-based virus inactivators. Here we have highlighted recent progress in developing PPVIs against several important enveloped viruses, including HIV, influenza virus, Zika virus (ZIKV), dengue virus (DENV), and herpes simplex virus (HSV), and the potential use of PPVIs for urgent treatment of infection by newly emerging or re-emerging viruses.Since intracellular survival of all chlamydiae depends on the manipulation of the host cell through type III secreted effector proteins, their characterization is crucial for the understanding of chlamydial pathogenesis. We functionally characterized the putative type III secreted Chlamydia abortus protein CAB063, describe its intracellular localization and identified pro- and eukaryotic binding partners. Based on an experimental infection model and plasmid transfections, we investigated the subcellular localization of CAB063 by immunofluorescence microscopy, immunoelectron microscopy, and Western blot analysis. Pro- and eukaryotic targets were identified by co-immunofluorescence, co-immunoprecipitation, and mass spectrometry. Transmission electron microscopy and flow cytometry were used for morphological and functional investigations on host cell apoptosis. CAB063 localized in the nuclear membrane of the host cell nucleus and we identified the chaperone HSP70 and lamin A/C as pro- and eukaryotic targets, respectively. CAB063-dependent morphological alterations of the host cell nucleus correlated with increased apoptosis rates of infected and CAB063-transfected cells. We provide evidence that CAB063 is a chaperone-folded type III secreted C. abortus virulence factor that targets lamin thereby altering the host cell nuclear membrane structure. This process may be responsible for an increased apoptosis rate at the end of the chlamydial developmental cycle, at which CAB063 is physiologically expressed.Healthy soil microbiomes are crucial for achieving high productivity in combination with crop quality, but our understanding of microbial diversity is still limited. In a large-scale study including 116 composite samples from vineyards, orchards and other crops from all over Styria (south-east Austria), agricultural management as well as distinct soil parameters were identified as drivers of the indigenous microbial communities in agricultural soils. The analysis of the soil microbiota based on microbial profiling of prokaryotic 16S rRNA gene fragments and fungal ITS regions revealed high bacterial and fungal diversity within Styrian agricultural soils; 206,596 prokaryotic and 53,710 fungal OTUs. Vineyards revealed a significantly higher diversity and distinct composition of soil fungi over orchards and other agricultural soils, whereas the prokaryotic diversity was unaffected. Soil pH was identified as one of the most important edaphic modulators of microbial community structure in both, vineyard and orchardThese findings provide the basis to adapt soil management practices in the future in order to maintain a healthy microbiome in agricultural soils.[This corrects the article DOI 10.3389/fmicb.2019.03039.].Phytoplankton are major contributors to labile organic matter in the upper ocean. Diverse heterotrophic bacteria successively metabolize these labile compounds and drive elemental biogeochemical cycling. We investigated the bioavailability of Synechococcus-derived organic matter (SOM) by estuarine and coastal microbes during 180-day dark incubations. Variations in organic carbon, inorganic nutrients, fluorescent dissolved organic matter (FDOM), and total/active microbial communities were monitored. The entire incubations could be partitioned into three phases (labeled I, II, and III) based on the total organic carbon (TOC) consumption rates of 6.38-7.01, 0.53-0.64, and 0.10-0.13 μmol C L-1 day-1, respectively. This corresponded with accumulation processes of NH4 +, NO2 -, and NO3 -, respectively. One tryptophan-like (C1) and three humic-like (C2, C3, and C4) FDOM components were identified. The intensity variation of C1 followed bacterial growth activities, and C2, C3, and C4 displayed labile, semi-labile, and refractory DOM characteristics, respectively. Alphaproteobacteria, Gammaproteobacteria, Bacteroidetes, and Actinobacteria dominated the quickly consumed process of SOM (phase I) coupled with a substantial amount of NH4 + generation. https://www.selleckchem.com/products/kpt-9274.html Thaumarchaeota became an abundant population with the highest activities in phase II, especially in the free-living size-fraction, and these organisms could perform chemoautotroph processes through the ammonia oxidation. Microbial populations frequently found in the dark ocean, even the deep sea, became abundant during phase III, in which Nitrospinae/Nitrospirae obtained energy through nitrite oxidation. Our results shed light on the transformation of different biological availability of organic carbon by coastal microorganisms which coupled with the regeneration of different form of inorganic nitrogen.The negative effects of honey bee parasitic mites and deformed wing virus (DWV) on honey bee and colony health have been well characterized. However, the relationship between DWV and mites, particularly viral replication inside the mites, remains unclear. Furthermore, the physiological outcomes of honey bee immune responses stimulated by DWV and the mite to the host (honey bee) and perhaps the pathogen/parasite (DWV/mite) are not yet understood. To answer these questions, we studied the tripartite interactions between the honey bee, Tropilaelaps mercedesae, and DWV as the model. T. mercedesae functioned as a vector for DWV without supporting active viral replication. Thus, DWV negligibly affected mite fitness. Mite infestation induced mRNA expression of antimicrobial peptides (AMPs), Defensin-1 and Hymenoptaecin, which correlated with DWV copy number in honey bee pupae and mite feeding, respectively. Feeding T. mercedesae with fruit fly S2 cells heterologously expressing honey bee Hymenoptaecin significantly downregulated mite Vitellogenin expression, indicating that the honey bee AMP manipulates mite reproduction upon feeding on bee.
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