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https://www.readbyqxmd.com/read/28214171/g-protein-based-elisa-as-a-potency-test-for-rabies-vaccines
#1
Martine Chabaud-Riou, Nadège Moreno, Fabien Guinchard, Marie Claire Nicolai, Elisabeth Niogret-Siohan, Nicolas Sève, Catherine Manin, Françoise Guinet-Morlot, Patrice Riou
The NIH test is currently used to assess the potency of rabies vaccine, a key criterion for vaccine release. This test is based on mice immunization followed by intracerebral viral challenge. As part of global efforts to reduce animal experimentation and in the framework of the development of Sanofi Pasteur next generation, highly-purified vaccine, produced without any material of human or animal origin, we developed an ELISA as an alternative to the NIH test. This ELISA is based on monoclonal antibodies recognizing specifically the native form of the viral G-protein, the major antigen that induces neutralizing antibody response to rabies virus...
February 14, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28213165/hbvcircle-a-novel-tool-to-investigate-hepatitis-b-virus-covalently-closed-circular-dna
#2
Zhipeng Yan, Jing Zeng, Youjun Yu, Kunlun Xiang, Hui Hu, Xue Zhou, Lili Gu, Li Wang, Jie Zhao, John A T Young, Lu Gao
BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as a stable episome in infected hepatocytes and serves as a template for the transcription of all viral genes. Due to the narrow host range of HBV, the development of a robust mouse model that supports cccDNA-dependent viral replication is a key hurdle in the development of novel HBV therapeutics. This study aimed to develop a novel tool to investigate HBV cccDNA. METHODS: Through minicircle technology, HBVcircle, a recombinant cccDNA, was easily generated and extracted from a genetically engineered E...
February 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28212737/gene-delivery-of-apoptin-derived-peptide-using-an-adeno-associated-virus-vector-inhibits-glioma-and-prolongs-animal-survival
#3
Xiuli Zhong, Hengyu Zhao, Songhe Liang, DanYang Zhou, Wenjia Zhang, Lijie Yuan
Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of the secreted HSP70-targeted peptide APOPTIN derived from Apoptin to GBM tumors. We applied this therapy to GBM models using human U87MG glioma cells and GBM xenograft models in mice. In U87MG and U251MG cells, conditioned medium from AAV2-apoptin-derived peptide (ADP)-expressing cells induced 83% and 78% cell death. In mice bearing intracranial U87MG tumors treated with AAV2-ADP, treatment resulted in a significant decrease in tumor growth and longer survival in mice bearing orthotopic invasive GBM brain tumors...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212352/rta-occupancy-of-the-origin-of-lytic-replication-during-murine-gammaherpesvirus-68-reactivation-from-b-cell-latency
#4
Alexis L Santana, Darby G Oldenburg, Varvara Kirillov, Laraib Malik, Qiwen Dong, Roman Sinayev, Kenneth B Marcu, Douglas W White, Laurie T Krug
RTA, the viral Replication and Transcription Activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. Lipopolysaccharide (LPS)/toll-like receptor (TLR)4 engagement enhances rhadinovirus reactivation. We developed two new systems to examine the interaction of RTA with host NF-kappaB (NF-κB) signaling during murine gammaherpesvirus 68 (MHV68) infection: a latent B cell line (HE-RIT) inducible for RTA-Flag expression and virus reactivation; and a recombinant virus (MHV68-RTA-Bio) that enabled in vivo biotinylation of RTA in BirA transgenic mice...
February 16, 2017: Pathogens
https://www.readbyqxmd.com/read/28211908/the-n-terminal-domain-of-schmallenberg-virus-envelope-protein-gc-is-highly-immunogenic-and-can-provide-protection-from-infection
#5
Kerstin Wernike, Andrea Aebischer, Gleyder Roman-Sosa, Martin Beer
Schmallenberg virus (SBV) is transmitted by insect vectors, and therefore vaccination is one of the most important tools of disease control. In our study, novel subunit vaccines on the basis of an amino-terminal domain of SBV Gc of 234 amino acids ("Gc Amino") first were tested and selected using a lethal small animal challenge model and then the best performing formulations also were tested in cattle. We could show that neither E. coli expressed nor the reduced form of "Gc Amino" protected from SBV infection...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210631/immunogenicity-and-cross-protection-in-mice-afforded-by-pandemic-h1n1-live-attenuated-influenza-vaccine-containing-wild-type-nucleoprotein
#6
Andrey Rekstin, Irina Isakova-Sivak, Galina Petukhova, Daniil Korenkov, Igor Losev, Tatiana Smolonogina, Tatiana Tretiak, Svetlana Donina, Svetlana Shcherbik, Tatiana Bousse, Larisa Rudenko
Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28210503/strongyloidiasis-current-status-with-emphasis-in-diagnosis-and-drug-research
#7
REVIEW
Tiago Mendes, Karen Minori, Marlene Ueta, Danilo Ciccone Miguel, Silmara Marques Allegretti
Strongyloidiasis is a parasitic neglected disease caused by the nematode Strongyloides stercoralis affecting 30 to 100 million people worldwide. Complications, strongly associated with alcoholism, organ transplants, and HTLV-1 virus, often arise due to late diagnosis, frequently leading to patient death. Lack of preemptive diagnosis is not the only difficulty when dealing with this parasite, since there are no gold standard diagnostic techniques, and the ones used have problems associated with sensitivity, resulting in false negatives...
2017: Journal of Parasitology Research
https://www.readbyqxmd.com/read/28209182/mesenchymal-stem-cells-alleviate-japanese-encephalitis-virus-induced-neuroinflammation-and-mortality
#8
Peiyu Bian, Chuantao Ye, Xuyang Zheng, Jing Yang, Wei Ye, Yuan Wang, Yun Zhou, Hongwei Ma, Peijun Han, Hai Zhang, Ying Zhang, Fanglin Zhang, Yingfeng Lei, Zhansheng Jia
BACKGROUND: Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia. Japanese encephalitis (JE) caused by JEV is characterized by extensive inflammatory cytokine secretion, microglia activation, blood-brain barrier (BBB) breakdown, and neuronal death, all of which contribute to the vicious cycle of inflammatory damage. There are currently no effective treatments for JE. Mesenchymal stem cells (MSCs) have been demonstrated to have a therapeutic effect on many central nervous system (CNS) diseases by regulating inflammation and other mechanisms...
February 16, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28208151/bacillus-calmette-gu%C3%A3-rin-confers-neuroprotection-in-a-murine-model-of-japanese-encephalitis
#9
Sahil Kulkarni, Sandeepan Mukherjee, Anupama Pandey, Ritwik Dahake, Usha Padmanabhan, Abhay S Chowdhary
OBJECTIVE: Japanese encephalitis (JE) is a debilitating disease caused by infection with the JE virus (JEV; family: Flaviviridae), which leaves neurological sequelae in survivors but more often leads to mortality. Neurodegeneration caused by inflammation is the primary pathology behind the clinical manifestation of encephalitis caused by JEV. Bacillus Calmette-Guérin (BCG) has been used in immunoprophylaxis for tuberculosis and in the adjuvant therapy of many malignancies, and has exhibited neuroprotective activities in experimental models of Parkinson and Alzheimer disease...
February 17, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28207910/a-single-mutation-in-the-envelope-protein-modulates-flavivirus-antigenicity-stability-and-pathogenesis
#10
Leslie Goo, Laura A VanBlargan, Kimberly A Dowd, Michael S Diamond, Theodore C Pierson
The structural flexibility or 'breathing' of the envelope (E) protein of flaviviruses allows virions to sample an ensemble of conformations at equilibrium. The molecular basis and functional consequences of virus conformational dynamics are poorly understood. Here, we identified a single mutation at residue 198 (T198F) of the West Nile virus (WNV) E protein domain I-II hinge that regulates virus breathing. The T198F mutation resulted in a ~70-fold increase in sensitivity to neutralization by a monoclonal antibody targeting a cryptic epitope in the fusion loop...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28207896/rna-seq-analysis-of-chikungunya-virus-infection-and-identification-of-granzyme-a-as-a-major-promoter-of-arthritic-inflammation
#11
Jane A C Wilson, Natalie A Prow, Wayne A Schroder, Jonathan J Ellis, Helen E Cumming, Linden J Gearing, Yee Suan Poo, Adam Taylor, Paul J Hertzog, Francesca Di Giallonardo, Linda Hueston, Roger Le Grand, Bing Tang, Thuy T Le, Joy Gardner, Suresh Mahalingam, Pierre Roques, Phillip I Bird, Andreas Suhrbier
: Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection), acute arthritis (day 7) and chronic disease (day 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28205605/the-role-of-the-rna-demethylase-fto-fat-mass-and-obesity-associated-and-mrna-methylation-in-hippocampal-memory-formation
#12
Brandon J Walters, Valentina Mercaldo, Colleen J Gillon, Matthew Yip, Rachael L Neve, Frederick M Boyce, Paul W Frankland, Sheena A Josselyn
The formation of long-lasting memories requires coordinated changes in gene expression and protein synthesis (Davis and Squire, 1984; Duvarci et al, 2008; Hernandez and Abel, 2008). Although many studies implicate DNA modifications (DNA methylation, histone modifications) in memory formation, the contributions of RNA modifications remain largely unexplored. Here, we investigated the role of mRNA methylation in hippocampal-dependent memory formation in mice. RNA modifications are highly dynamic and readily reversible (Jia et al, 2013)...
February 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28203239/sublingual-priming-with-a-hiv-gp41-based-subunit-vaccine-elicits-mucosal-antibodies-and-persistent-b-memory-responses-in-non-human-primates
#13
Selma Bekri, Pierre Bourdely, Carmelo Luci, Nathalie Dereuddre-Bosquet, Bin Su, Frédéric Martinon, Véronique M Braud, Irene Luque, Pedro L Mateo, Sara Crespillo, Francisco Conejero-Lara, Christiane Moog, Roger Le Grand, Fabienne Anjuère
Persistent B cell responses in mucosal tissues are crucial to control infection against sexually transmitted pathogens like human immunodeficiency virus 1 (HIV-1). The genital tract is a major site of infection by HIV. Sublingual (SL) immunization in mice was previously shown to generate HIV-specific B cell immunity that disseminates to the genital tract. We report here the immunogenicity in female cynomolgus macaques of a SL vaccine based on a modified gp41 polypeptide coupled to the cholera toxin B subunit designed to expose hidden epitopes and to improve mucosal retention...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28202388/viral-vector-reprogramming-of-adult-resident-striatal-oligodendrocytes-into-functional-neurons
#14
Marc S Weinberg, Hugh E Criswell, Sara K Powell, Aadra P Bhatt, Thomas J McCown
Recent advances suggest that in vivo reprogramming of endogenous cell populations provides a viable alternative for neuron replacement. Astrocytes and oligodendrocyte precursor cells can be induced to transdifferentiate into neurons in the CNS, but, in these instances, reprogramming requires either transgenic mice or retroviral-mediated gene expression. We developed a microRNA (miRNA)-GFP construct that in vitro significantly reduced the expression of polypyrimidine tract-binding protein, and, subsequently, we packaged this construct in a novel oligodendrocyte preferring adeno-associated virus vector...
February 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28199846/frequent-zika-virus-sexual-transmission-and-prolonged-viral-rna-shedding-in-an-immunodeficient-mouse-model
#15
Nisha K Duggal, Jana M Ritter, Samuel E Pestorius, Sherif R Zaki, Brent S Davis, Gwong-Jen J Chang, Richard A Bowen, Aaron C Brault
Circulation of Zika virus (ZIKV) was first identified in the Western hemisphere in late 2014. Primarily transmitted through mosquito bite, ZIKV can also be transmitted through sex and from mother to fetus, and maternal ZIKV infection has been associated with fetal malformations. We assessed immunodeficient AG129 mice for their capacity to shed ZIKV in semen and to infect female mice via sexual transmission. Infectious virus was detected in semen between 7 and 21 days post-inoculation, and ZIKV RNA was detected in semen through 58 days post-inoculation...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28198699/longitudinal-imaging-of-hiv-1-spread-in-humanized-mice-with-parallel-3d-immunofluorescence-and-electron-tomography
#16
Collin Kieffer, Mark S Ladinsky, Allen Ninh, Rachel P Galimidi, Pamela J Bjorkman
Dissemination of HIV-1 throughout lymphoid tissues leads to systemic virus spread following infection. We combined tissue clearing, 3D-immunofluorescence, and electron tomography (ET) to longitudinally assess early HIV-1 spread in lymphoid tissues in humanized mice. Immunofluorescence revealed peak infection density in gut at 10-12 days post-infection when blood viral loads were low. Human CD4+ T-cells and HIV-1-infected cells localized predominantly to crypts and the lower third of intestinal villi. Free virions and infected cells were not readily detectable by ET at 5-days post-infection, whereas HIV-1-infected cells surrounded by pools of free virions were present in ~10% of intestinal crypts by 10-12 days...
February 15, 2017: ELife
https://www.readbyqxmd.com/read/28197304/ester-prodrugs-of-ihvr-19029-with-enhanced-oral-exposure-and-prevention-of-gastrointestinal-glucosidase-interaction
#17
Julia Ma, Shuo Wu, Xuexiang Zhang, Fang Guo, Katherine Yang, Jia Guo, Qing Su, Huagang Lu, Patrick Lam, Yuhuan Li, Zhengyin Yan, William Kinney, Ju-Tao Guo, Timothy M Block, Jinhong Chang, Yanming Du
IHVR-19029 (6) is a lead endoplasmic reticulum α-glucosidases I and II inhibitor, which efficiently protected mice from lethal Ebola and Marburg virus infections via injection route, but suffered from low bioavailability and off-target interactions with gut glucosidases when administered orally. In an effort to improve efficacious exposure levels and avoid side effects, we designed and synthesized ester prodrugs. Not only were the prodrugs stable in simulated gastric and intestinal fluids and were inactive against glucosidases but they also exhibited antiviral activities against dengue virus infection in a cell based assay...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196762/enteric-helminth-induced-type-i-interferon-signalling-protects-against-pulmonary-virus-infection-through-interaction-with-the-microbiota
#18
Amanda J McFarlane, Henry J McSorley, Donald J Davidson, Paul M Fitch, Claire Errington, Karen J Mackenzie, Eva S Gollwitzer, Chris J C Johnston, Andrew S MacDonald, Michael R Edwards, Nicola L Harris, Benjamin J Marsland, Rick M Maizels, Jürgen Schwarze
BACKGROUND: Helminth parasites have been reported to have beneficial immune modulatory effects in allergic and autoimmune conditions and detrimental consequences in tuberculosis and some viral infections. Their role in co-infection with respiratory viruses is not clear. OBJECTIVE: Here, we investigated the effects of strictly enteric helminth infection with Heligmosomoides polygyrus on respiratory syncytial virus (RSV) infection in a mouse model. METHODS: A murine helminth/ RSV co-infection model was developed...
February 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28195529/suppressor-of-cytokine-signaling-socs-5-ameliorates-influenza-infection-via-inhibition-of-egfr-signaling
#19
Lukasz Kedzierski, Michelle D Tate, Alan C Hsu, Tatiana B Kolesnik, Edmond M Linossi, Laura Dagley, Zhaoguang Dong, Sarah Freeman, Giuseppe Infusini, Malcolm R Starkey, Nicola L Bird, Simon M Chatfield, Jeffrey J Babon, Nicholas Huntington, Gabrielle Belz, Andrew Webb, Peter Ab Wark, Nicos A Nicola, Jianqing Xu, Katherine Kedzierska, Philip M Hansbro, Sandra E Nicholson
Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) 5 has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss...
February 14, 2017: ELife
https://www.readbyqxmd.com/read/28195035/pre-s2-mutant-induced-mammalian-target-of-rapamycin-signal-pathways-as-potential-therapeutic-targets-for-hepatitis-b-virus-associated-hepatocellular-carcinoma
#20
Chiao-Fang Teng, Han-Chieh Wu, Woei-Cherng Shyu, Long-Bin Jeng, Ih-Jen Su
Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Pre-S2 mutant represents an HBV oncoprotein that is accumulated in the endoplasmic reticulum (ER) and manifests as type II ground glass hepatocytes (GGHs). Pre-S2 mutant can induce ER stress and initiate multiple ER stress-dependent or -independent cellular signal pathways, leading to growth advantage of type II GGH. Importantly, the mammalian target of rapamycin (mTOR) signal pathways are consistently activated throughout the liver tumorigenesis in pre-S2 mutant transgenic mice and in human HCC tissues, leading to hepatocyte proliferation, metabolic disorders, and HCC tumorigenesis...
February 14, 2017: Cell Transplantation
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