scholarly journals SNAP47 Interacts with ATG14 to Promote VP1 Conjugation and CVB3 Propagation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2141
Author(s):  
Pinhao Xiang ◽  
Yasir Mohamud ◽  
Honglin Luo
Keyword(s):  
Cellular Membrane ◽  
Viral Capsid ◽  
Human Pathogen ◽  
Cell Models ◽  
Membrane Fusion Protein ◽  
Protein Levels ◽  
Cvb3 Infection ◽  
The Family ◽  
Capsid Protein Vp1 ◽  
Disulfide Interactions

Coxsackievirus B3 (CVB3), an enterovirus (EV) in the family of Picornaviridae, is a global human pathogen for which effective antiviral treatments and vaccines are lacking. Previous research demonstrated that EV-D68 downregulated the membrane fusion protein SNAP47 (synaptosome associated protein 47) and SNAP47 promoted EV-D68 replication via regulating autophagy. In the current study, we investigated the interplay between CVB3 and cellular SNAP47 using HEK293T/HeLa cell models. We showed that, upon CVB3 infection, protein levels of SNAP47 decreased independent of the activity of virus-encoded proteinase 3C. We further demonstrated that the depletion of SNAP47 inhibited CVB3 infection, indicating a pro-viral function of SNAP47. Moreover, we found that SNAP47 co-localizes with the autophagy-related protein ATG14 on the cellular membrane fractions together with viral capsid protein VP1, and expression of SNAP47 or ATG14 enhanced VP1 conjugation. Finally, we revealed that disulfide interactions had an important role in strengthening VP1 conjugation. Collectively, our study elucidated a mechanism by which SNAP47 and ATG14 promoted CVB3 propagation through facilitating viral capsid assembly.

scholarly journals Characterization and phosphoproteomic analysis of a human immortalized podocyte model of Fabry disease generated using CRISPR/Cas9 technology

2016 ◽  
Vol 311 (5) ◽  
pp. F1015-F1024 ◽  
Author(s):  
Ester M. Pereira ◽  
Anatália Labilloy ◽  
Megan L. Eshbach ◽  
Ankita Roy ◽  
Arohan R. Subramanya ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Human Kidney ◽  
Premature Death ◽  
Antibody Array ◽  
Cell Models ◽  
Lysosomal Storage ◽  
Protein Levels ◽  
Gla Gene ◽  
Fabry Nephropathy ◽  
And Control

Fabry nephropathy is a major cause of morbidity and premature death in patients with Fabry disease (FD), a rare X-linked lysosomal storage disorder. Gb3, the main substrate of α-galactosidase A (α-Gal A), progressively accumulates within cells in a variety of tissues. Establishment of cell models has been useful as a tool for testing hypotheses of disease pathogenesis. We applied CRISPR/Cas9 genome editing technology to the GLA gene to develop human kidney cell models of FD in human immortalized podocytes, which are the main affected renal cell type. Our podocytes lack detectable α-Gal A activity and have increased levels of Gb3. To explore different pathways that could have distinct patterns of activation under conditions of α-gal A deficiency, we used a high-throughput antibody array to perform phosphorylation profiling of CRISPR/Cas9-edited and control podocytes. Changes in both total protein levels and in phosphorylation status per site were observed. Analysis of our candidate proteins suggests that multiple signaling pathways are impaired in FD.

scholarly journals Edwardsiella tardaEndocarditis Confirmed by Indium-111 White Blood Cell Scan: An Unusual Pathogen and Diagnostic Modality

2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Kayleigh M. Litton ◽  
Bret A. Rogers
Keyword(s):  
Blood Cell ◽  
White Blood Cell ◽  
Imaging Modality ◽  
Edwardsiella Tarda ◽  
Human Pathogen ◽  
Diagnostic Modality ◽  
Prosthetic Aortic Valve ◽  
Wide Range ◽  
The Family ◽  
Indium 111

Edwardsiella tardais a freshwater marine member of the family Enterobacteriaceae which often colonizes fish, lizards, snakes, and turtles but is an infrequent human pathogen. Indium-111- (111In-) labeled white blood cell (WBC) scintigraphy is an imaging modality which has a wide range of reported sensitivity and specificity (from 60 to 100% and from 68 to 92%, resp.) for diagnosing acute and chronic infection. We describe a case of suspectedE. tardaprosthetic aortic valve and mitral valve endocarditis with probable vegetations and new mitral regurgitation on transthoracic and transesophageal echocardiograms which was supported with the use of111In-labeled WBC scintigraphy.

scholarly journals Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

2006 ◽  
Vol 63 (6) ◽  
pp. 545-551 ◽  
Author(s):  
Marina Vuceljic ◽  
Gordana Zunic ◽  
Predrag Romic ◽  
Miodrag Jevtic
Keyword(s):  
Total Protein ◽  
Injury Severity ◽  
Venous Blood ◽  
Early Period ◽  
Cellular Membrane ◽  
Protein Levels ◽  
Oxidative Damages ◽  
Gradual Development ◽  
Initial Injury ◽  
Initial Severity

Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA), as an indicator of lipid peroxidation, and osmolal gap (OG), as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52), injured during the bombing with the Injury Severity Score (ISS) ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24) and a group of severely (ISS ? 26, n = 28) injured males. The uninjured volunteers (n = 10) were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01), while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

scholarly journals Dynamic proteomics of HSV1 infection reveals molecular events that govern non-stochastic infection outcomes

2016 ◽  
Author(s):  
Nir Drayman ◽  
Omer Karin ◽  
Avi Mayo ◽  
Tamar Danon ◽  
Lev Shapira ◽  
...  
Keyword(s):  
Single Cells ◽  
Infection Process ◽  
Human Pathogen ◽  
Herpes Simplex Virus 1 ◽  
Host Interactions ◽  
Protein Levels ◽  
Molecular Events ◽  
Proteomics Approach ◽  
Infected Cells ◽  
Simplex Virus

AbstractViral infection is usually studied at the level of cell populations, averaging over hundreds of thousands of individual cells. Moreover, measurements are typically done by analyzing a few time points along the infection process. While informative, such measurements are limited in addressing how cell variability affects infection outcome. Here we employ dynamic proteomics to study virus-host interactions, using the human pathogen Herpes Simplex virus 1 as a model. We tracked >50,000 individual cells as they respond to HSV1 infection, allowing us to model infection kinetics and link infection outcome (productive or not) with the cell state at the time of initial infection. We find that single cells differ in their preexisting susceptibility to HSV1, and that this is partially mediated by their cell-cycle position. We also identify specific changes in protein levels and localization in infected cells, attesting to the power of the dynamic proteomics approach for studying virus-host interactions.

scholarly journals Antibody escape by polyomavirus capsid mutation facilitates neurovirulence

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Matthew D Lauver ◽  
Daniel J Goetschius ◽  
Colleen S Netherby-Winslow ◽  
Katelyn N Ayers ◽  
Ge Jin ◽  
...  
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Capsid Protein ◽  
Neutralizing Antibody ◽  
Viral Capsid ◽  
Cell Tropism ◽  
Capsid Protein Vp1 ◽  
Particle Refinement ◽  
Immunomodulatory Therapies ◽  
Major Viral Capsid Protein

JCPyV polyomavirus, a member of the human virome, causes progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo-EM and a custom sub-particle refinement approach, we resolved an MuPyV:Fab complex map to 3.2 Å resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation.

scholarly journals Genogroup II Noroviruses Efficiently Bind to Heparan Sulfate Proteoglycan Associated with the Cellular Membrane

2004 ◽  
Vol 78 (8) ◽  
pp. 3817-3826 ◽  
Author(s):  
Masaru Tamura ◽  
Katsuro Natori ◽  
Masahiko Kobayashi ◽  
Tatsuo Miyamura ◽  
Naokazu Takeda
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Cellular Membrane ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
Sulfated Glycosaminoglycan ◽  
The Family ◽  
Sulfated Derivative ◽  
Causative Agents

ABSTRACT Norovirus (NV), a member of the family Caliciviridae, is one of the important causative agents of acute gastroenteritis. In the present study, we found that virus-like particles (VLPs) derived from genogroup II (GII) NV were bound to cell surface heparan sulfate proteoglycan. Interestingly, the VLPs derived from GII were more than ten times likelier to bind to cells than were those derived from genogroup I (GI). Heparin, a sulfated glycosaminoglycan, and suramin, a highly sulfated derivative of urea, efficiently blocked VLP binding to mammalian cell surfaces. The reagents known to bind to cell surface heparan sulfate, as well as the enzymes that specifically digest heparan sulfate, markedly reduced VLP binding to the cells. Treatment of the cells with chlorate revealed that sulfation of heparan sulfate plays an important role in the NV-heparan sulfate interaction. The binding efficiency of NV to undifferentiated Caco-2 (U-Caco-2) cells differed largely between GI NV and GII NV, whereas the efficiency of binding to differentiated Caco-2 (D-Caco-2) cells did not differ significantly between the two genogroups, although slight differences between strains were observed. Digestion with heparinase I resulted in a reduction of up to 90% in U-Caco-2 cells and a reduction of up to only 50% in D-Caco-2 cells, indicating that heparan sulfate is the major binding molecule for U-Caco-2 cells, while it contributed to only half of the binding in the case of D-Caco-2 cells. The other half of those VLPs was likely to be associated with H-type blood antigen, suggesting that GII NV has two separate binding sites. The present study is the first to address the possible role of cell surface glycosaminoglycans in the binding of recombinant VLPs of NV.

Serratia marcescens Infections

1986 ◽  
Vol 7 (5) ◽  
pp. 273-280 ◽  
Author(s):  
Jacques F. Acar
Keyword(s):  
Serratia Marcescens ◽  
Clinical Laboratory ◽  
Clinical Specimen ◽  
Human Pathogen ◽  
The Family ◽  
Opportunistic Human Pathogen

The recognition of serratia as an opportunistic human pathogen can be dated from 1959, when the microorganism entered the family of Enterobacteriaceae, with features recognizable in the clinical laboratory and related to the Klebsiella/Enterobacter group. Since then, physicians have been challenged to establish the significance of isolation of serratia from a clinical specimen.

Serratia no longer an opportunistic uncommon pathogen – case series & review of literature

2021 ◽  
Vol 21 ◽  
Author(s):  
Varsha Gupta ◽  
Shiwani Sharma ◽  
Kritika Pal ◽  
Poonam Goyal ◽  
Deepak Agarwal ◽  
...  
Keyword(s):  
Serratia Marcescens ◽  
Case Series ◽  
Opportunistic Pathogen ◽  
Morphological Characters ◽  
Enteric Bacterium ◽  
Human Pathogen ◽  
Review Of Literature ◽  
Medical College ◽  
Serious Infections ◽  
The Family

Background: Serratia spp. is a common enteric bacterium generally thought not to be pathogenic in the gastrointestinal tract. Serratia marcescens is a member of the genus Serratia, which is a part of the family Enterobacteriales..Of all Serratia species, S. marcescens is the most common clinical isolate and the most important human pathogen. Objective: We are discussing here four cases of Serratia marcescens which we reported in our laboratory in the Department of Microbiology Government Medical College and Hospital Chandigarh during six months of duration. Method: All the samples were processed and identified as per standard microbiological techniques.The isolates of Serratia marcescens were identified, depending upon their biochemical and morphological characters and further confirmed by MALDI-TOF-MS ,PGIMER Chandigarh. Result: In one of the four cases there was polymicrobial infection and one patient was diabetic and rest three patients were immunocompetent. The importance of detection and reporting of Serratia marcescens is related to the concern regarding its increase spread in hospital settings as nosocomial infection . Conclusion: We need to identify and isolate this pathogen ,not thinking of only contaminant and opportunistic pathogen but as a pathogen which can lead to serious infections in hospital settings .

Murine Ifit3 restricts the replication of Rabies virus both in vitro and in vivo

2021 ◽  
Vol 102 (7) ◽  
Author(s):  
Benjie Chai ◽  
Dayong Tian ◽  
Ming Zhou ◽  
Bin Tian ◽  
Yueming Yuan ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Cultured Cells ◽  
Immune Defence ◽  
Tetratricopeptide Repeats ◽  
Protein Levels ◽  
The Family ◽  
Deficient Mice ◽  
Insight Into

Rabies virus (RABV) infection can initiate the host immune defence response and induce an antiviral state characterized by the expression of interferon (IFN)-stimulated genes (ISGs), among which the family of genes of IFN-induced protein with tetratricopeptide repeats (Ifits) are prominent representatives. Herein, we demonstrated that the mRNA and protein levels of Ifit1, Ifit2 and Ifit3 were highly increased in cultured cells and mouse brains after RABV infection. Recombinant RABV expressing Ifit3, designated rRABV-Ifit3, displayed a lower pathogenicity than the parent RABV in C57BL/6 mice after intramuscular administration, and Ifit3-deficient mice exhibited higher susceptibility to RABV infection and higher mortality during RABV infection. Moreover, compared with their individual expressions, co-expression of Ifit2 and Ifit3 could more effectively inhibit RABV replication in vitro. These results indicate that murine Ifit3 plays an essential role in restricting the replication and reducing the pathogenicity of RABV. Ifit3 acts synergistically with Ifit2 to inhibit RABV replication, providing further insight into the function and complexity of the Ifit family.

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