Herpesviruses and the Type Ⅲ Interferon System

Type Ⅲ interferons (IFNs) represent the most recently discovered group of IFNs.Together with type Ⅰ IFNs (e.g.IFN-α/β),type Ⅲ IFNs (IFN-λ) are produced as part of the innate immune response to virus infection,and elicit an anti-viral state by inducing expression of interferon stimulated genes (ISGs).It was initially thought that type Ⅰ IFNs and type Ⅲ IFNs perform largely redundant functions.However,it has become evident that type Ⅲ IFNs particularly play a major role in antiviral protection of mucosal epithelial barriers,thereby serving an important role in the first-line defense against virus infection and invasion at contact areas with the outside world,versus the generally more broad,potent and systemic antiviral effects of type Ⅰ IFNs.Herpesviruseses are large DNA viruses,which enter their host via mucosal surfaces and establish lifelong,latent infections.Despite the importance of mucosal epithelial cells in the pathogenesis of herpesviruses,our current knowledge on the interaction of herpesviruses with type Ⅲ IFN is limited and largely restricted to studies on the alphaherpesvirus herpes simplex virus (HSV).This review summarizes the current understanding about the role of IFN-λ in the immune response against herpesvirus infections.     

Gastric epithelial cell death caused by Helicobacter suis and Helicobacter pylori γ-glutamyl transpeptidase is mainly glutathione degradation-dependent

Helicobacter (H.) suis is the most prevalent non-H. pylori Helicobacter species colonizing the stomach of humans suffering from gastric disease. In the present study, we aimed to unravel the mechanism used by H. suis to induce gastric epithelial cell damage. H. suis lysate induced mainly apoptotic death of human gastric epithelial cells. Inhibition of γ-glutamyl transpeptidase (GGT) activity present in H. suis lysate and incubation of AGS cells with purified native and recombinant H. suis GGT showed that this enzyme was partly responsible for the observed apoptosis. Supplementation of H. suis or H. pylori GGT-treated cells with glutathione strongly enhanced the harmful effect of both enzymes and resulted in the induction of oncosis/necrosis, demonstrating that H. suis and H. pylori GGT-mediated degradation of glutathione and the resulting formation of glutathione degradation products play a direct and active role in the induction of gastric epithelial cell death. This was preceded by an increase of extracellular H(2)O(2) concentrations, generated in a cell-independent manner and causing lipid peroxidation. In conclusion, H. suis and H. pylori GGT-mediated generation of pro-oxidant glutathione degradation products brings on cell damage and causes apoptosis or necrosis, dependent on the amount of extracellular glutathione available as a GGT substrate.     

Automatic detection of the carotid artery boundary on cross-sectional MR image sequences using a circle model guided dynamic programming

Background  

Systematic aerobe training has positive effects on the compliance of dedicated arterial walls. The adaptations of the arterial structure and function are associated with the blood flow-induced changes of the wall shear stress which induced vascular remodelling via nitric oxide delivered from the endothelial cell. In order to assess functional changes of the common carotid artery over time in these processes, a precise measurement technique is necessary. Before this study, a reliable, precise, and quick method to perform this work is not present.     

Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages

Sialoadhesin is exclusively expressed on specific subpopulations of macrophages. Since sialoadhesin-positive macrophages are involved in inflammatory autoimmune diseases, such as multiple sclerosis, and potentially in the generation of immune responses, targeted delivery of drugs, toxins or antigens via sialoadhesin-specific immunoconjugates may prove a useful therapeutic strategy. Originally, sialoadhesin was characterized as a lymphocyte adhesion molecule, though recently its involvement in internalization of sialic acid carrying pathogens was shown, suggesting that sialoadhesin is an endocytic receptor. In this report, we show that porcine sialoadhesin-specific antibodies and F(ab'')₂ fragments trigger sialoadhesin internalization, both in primary porcine macrophages and in cells expressing recombinant porcine sialoadhesin. Using chemical inhibitors, double immunofluorescence stainings and dominant-negative constructs, porcine sialoadhesin internalization was shown to be clathrin- and Eps15-dependent and to result in targeting to early endosomes but not lysosomes. Besides characterizing the sialoadhesin endocytosis mechanism, two sialoadhesin-specific immunoconjugates were evaluated. We observed that porcine sialoadhesin-specific immunotoxins efficiently kill sialoadhesin-expressing macrophages. Furthermore, porcine sialoadhesin-specific albumin immunoconjugates were shown to be internalized in macrophages and immunization with these immunoconjugates resulted in a rapid and robust induction of albumin-specific antibodies, this compared to immunization with albumin alone. Together, these data expand sialoadhesin functionality and show that it can function as an endocytic receptor, a feature that cannot only be misused by sialic acid carrying pathogens, but that may also be used for specific targeting of toxins or antigens to sialoadhesin-expressing macrophages.     

Herpes simplex virus type 1 penetrates the basement membrane in human nasal respiratory mucosa

Background

Herpes simplex virus infections are highly prevalent in humans. However, the current therapeutics suffer important drawbacks such as limited results in neonates, increasing occurrence of resistance and impeded treatment of stromal infections. Remarkably, interactions of herpesviruses with human mucosa, the locus of infection, remain poorly understood and the underlying mechanisms in stromal infection remain controversial.

Methodology/Principal Findings

A human model consisting of nasal respiratory mucosa explants was characterised. Viability and integrity were examined during 96 h of cultivation. HSV1-mucosa interactions were analysed. In particular, we investigated whether HSV1 is able to reach the stroma.Explant viability and integrity remained preserved. HSV1 induced rounding up and loosening of epithelial cells with very few apoptotic and necrotic cells observed. Following 16–24 h of infection, HSV1 penetrated the basement membrane and replicated in the underlying lamina propria.

Conclusions/Significance

This human explant model can be used to study virus-mucosa interactions and viral mucosal invasion mechanisms. Using this model, our results provide a novel insight into the HSV1 stromal invasion mechanism and for the first time directly demonstrate that HSV1 can penetrate the basement membrane.     

Pseudorabies virus glycoprotein gD contains a functional endocytosis motif that acts in concert with an endocytosis motif in gB to drive internalization of antibody-antigen complexes from the surface of infected monocytes

Viral glycoproteins gB and gD of the swine alphaherpesvirus pseudorabies virus (PRV), which is closely related to human herpes simplex virus and varicella-zoster virus, are able to drive internalization of antibody-antigen complexes that may form at the cell surface of infected monocytes, thereby protecting these cells from efficient antibody-mediated lysis. We found earlier that gB relies on an endocytosis motif in its cytoplasmic domain for its function during this internalization process. Here, we report that the PRV gD protein also contains a functional endocytosis motif (YRLL) in its cytoplasmic domain that drives spontaneous endocytosis of gD from the cell surface early in infection and that acts in concert with the endocytosis motif in gB to contribute to efficient internalization of antibody-antigen complexes in PRV-infected monocytes.     

Antibody-induced and cytoskeleton-mediated redistribution and shedding of viral glycoproteins, expressed on pseudorabies virus-infected cells.

Fluorescein isothiocyanate-labeled porcine pseudorabies virus (PrV) polyclonal antibodies were added to PrV-infected swine kidney cells in vitro at 37 degrees C. In approximately 47% of the infected cells, the addition induced passive patching and subsequent energy- and microtubule-dependent capping of all viral envelope glycoproteins, expressed on the plasma membranes of the infected cells. Further contraction and extrusion of the capped viral glycoproteins occurred in approximately 30% of the capped cells 2 h after the addition of antibodies and was accompanied by a concentration of F-actin beneath the caps. At that time, about 18% of the extruded caps were shed spontaneously into the surrounding medium. Mechanical force released 85% of the extruded caps, leaving viable cells with no microscopically detectable levels of viral glycoproteins on their plasma membranes. Experiments with PrV deletion mutants showed that viral glycoproteins gE and gI are important in triggering viral glycoprotein redistribution. Since the PrV gE-gI complex exhibits Fc receptor activity which facilitates capping, the importance of gE and gI may be partially explained by antibody bipolar bridging.     

Distribution and conservation of mobile elements in the genus Drosophila

Essentially nothing is known of the origin, mode of transmission, and evolution of mobile elements within the genus Drosophila. To better understand the evolutionary history of these mobile elements, we examined the distribution and conservation of homologues to the P, I, gypsy, copia, and F elements in 34 Drosophila species from three subgenera. Probes specific for each element were prepared from D. melanogaster and hybridized to genomic DNA. Filters were washed under conditions of increasing stringency to estimate the similarity between D. melanogaster sequences and their homologues in other species. The I element homologues show the most limited distribution of all elements tested, being restricted to the melanogaster species group. The P elements are found in many members of the subgenus Sophophora but, with the notable exception of D. nasuta, are not found in the other two subgenera. Copia-, gypsy-, and F-element homologues are widespread in the genus, but their similarity to the D. melanogaster probe differs markedly between species. The distribution of copia and P elements and the conservation of the gypsy and P elements is inconsistent with a model that postulates a single ancient origin for each type of element followed by mating-dependent transmission. The data can be explained by horizontal transmission of mobile elements between reproductively isolated species.      

在韩国境内Potentilla fragarioides var.sprengeliana的遗传多样 …

根据２２个等位酶位点遗传变异,探讨了韩国境内委陵菜（Ｐｏｔｅｎｔｉｌｌａ ｆｒａｇａｒｉｏｉｄｅｓ Ｌ．ｖａｒ．ｓｐｒｅｎｇｅｌｉａｎａ）的遗传多样性和种群结构。酶位点的多态位点百分比为５９．１％。种和种群水平上的遗传多样性比较高,分别为Ｈｅｓ＝０．２１０,Ｈｅｐ＝０．１９９;而种群的分化水平则相对较低（ＧＳＴ＝０．０７４）。１９个种群中随机交配的偏差为ＦＩＳ＝０．３３１。每代迁移数的间接估计