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https://www.readbyqxmd.com/read/28521640/antibody-mediated-immunotherapy-against-chronic-hepatitis-b-virus-infection
#1
Ying Gao, Tian-Ying Zhang, Quan Yuan, Ning-Shao Xia
The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogues, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus...
May 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28513592/ifn-%C3%AE-increases-susceptibility-to-influenza-a-infection-through-suppression-of-group-ii-innate-lymphoid-cells
#2
D Califano, Y Furuya, S Roberts, D Avram, A N J McKenzie, D W Metzger
Increased levels of interferon-γ (IFN-γ) are routinely observed in the respiratory tract following influenza virus infection, yet its potential role remains unclear. We now demonstrate that influenza-induced IFN-γ restricts protective innate lymphoid cell group II (ILC2) function in the lung following challenge with the pandemic H1N1 A/CA/04/2009 (CA04) influenza virus. Specifically, IFN-γ deficiency resulted in enhanced ILC2 activity, characterized by increased production of interleukin (IL)-5 and amphiregulin, and improved tissue integrity, yet no change in ILC2 numbers, viral load or clearance...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28507081/reversion-of-anergy-signatures-in-clonal-cd21low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#3
Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM(+)CD27(+) B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21(low) phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28498373/genomic-exploration-of-individual-giant-ocean-viruses
#4
William H Wilson, Ilana C Gilg, Mohammad Moniruzzaman, Erin K Field, Sergey Koren, Gary R LeCleir, Joaquín Martínez Martínez, Nicole J Poulton, Brandon K Swan, Ramunas Stepanauskas, Steven W Wilhelm
Viruses are major pathogens in all biological systems. Virus propagation and downstream analysis remains a challenge, particularly in the ocean where the majority of their microbial hosts remain recalcitrant to current culturing techniques. We used a cultivation-independent approach to isolate and sequence individual viruses. The protocol uses high-speed fluorescence-activated virus sorting flow cytometry, multiple displacement amplification (MDA), and downstream genomic sequencing. We focused on 'giant viruses' that are readily distinguishable by flow cytometry...
May 12, 2017: ISME Journal
https://www.readbyqxmd.com/read/28497119/aedes-aegypti-piwi4-is-a-noncanonical-piwi-protein-involved-in-antiviral-responses
#5
Margus Varjak, Kevin Maringer, Mick Watson, Vattipally B Sreenu, Anthony C Fredericks, Emilie Pondeville, Claire L Donald, Jelle Sterk, Joy Kean, Marie Vazeille, Anna-Bella Failloux, Alain Kohl, Esther Schnettler
The small interfering RNA (siRNA) pathway is a major antiviral response in mosquitoes; however, another RNA interference pathway, the PIWI-interacting RNA (piRNA) pathway, has been suggested to be antiviral in mosquitoes. Piwi4 has been reported to be a key mediator of this response in mosquitoes, but it is not involved in the production of virus-specific piRNAs. Here, we show that Piwi4 associates with members of the antiviral exogenous siRNA pathway (Ago2 and Dcr2), as well as with proteins of the piRNA pathway (Ago3, Piwi5, and Piwi6) in an Aedes aegypti-derived cell line, Aag2...
May 2017: MSphere
https://www.readbyqxmd.com/read/28497117/rna-interference-restricts-rift-valley-fever-virus-in-multiple-insect-systems
#6
Isabelle Dietrich, Stephanie Jansen, Gamou Fall, Stephan Lorenzen, Martin Rudolf, Katrin Huber, Anna Heitmann, Sabine Schicht, El Hadji Ndiaye, Mick Watson, Ilaria Castelli, Benjamin Brennan, Richard M Elliott, Mawlouth Diallo, Amadou A Sall, Anna-Bella Failloux, Esther Schnettler, Alain Kohl, Stefanie C Becker
The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans and livestock by a large number of mosquito species. RNA interference (RNAi) has been characterized as an important innate immune defense mechanism used by mosquitoes to limit replication of positive-sense RNA flaviviruses and togaviruses; however, little is known about its role against negative-strand RNA viruses such as RVFV. We show that virus-specific small RNAs are produced in infected mosquito cells, in Drosophila melanogaster cells, and, most importantly, also in RVFV vector mosquitoes...
May 2017: MSphere
https://www.readbyqxmd.com/read/28495370/an-optimized-method-for-enumerating-cns-derived-memory-b-cells-during-viral-induced-inflammation
#7
Krista D DiSano, Stephen A Stohlman, Cornelia C Bergmann
BACKGROUND: CNS inflammation resulting from infection, injury, or neurodegeneration leads to accumulation of diverse B cell subsets. Although antibody secreting cells (ASC) within the inflamed CNS have been extensively examined, memory B cell (Bmem) characterization has been limited as they do not secrete antibody without stimulation. Moreover, unlike human Bmem, reliable surface markers for murine Bmem remain elusive. NEW METHOD: Using a viral encephalomyelitis model we developed a modified limiting dilution in vitro stimulation assay to convert CNS-derived virus specific Bmem into ASC...
May 8, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28483675/effector-cd8-t-cell-derived-interleukin-10-enhances-acute-liver-immunopathology
#8
Jessica Fioravanti, Pietro Di Lucia, Diletta Magini, Federica Moalli, Carolina Boni, Alexandre Pierre Benechet, Valeria Fumagalli, Donato Inverso, Andrea Vecchi, Amleto Fiocchi, Stefan Wieland, Robert Purcell, Carlo Ferrari, Francis V Chisari, Luca G Guidotti, Matteo Iannacone
BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8(+) T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and the role that IL-10 might play in liver disease is currently unknown. METHODS: This study involved mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV...
May 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28482908/curative-or-pre-emptive-adenovirus-specific-t-cell-transfer-from-matched-unrelated-or-third-party-haploidentical-donors-after-hsct-including-ucb-transplantations-a-successful-phase-i-ii-multicenter-clinical-trial
#9
Chongsheng Qian, Arnaud Campidelli, Yingying Wang, Huili Cai, Véronique Venard, Hélène Jeulin, Jean Hugues Dalle, Cécile Pochon, Maud D'aveni, Benedicte Bruno, Catherine Paillard, Stéphane Vigouroux, Charlotte Jubert, Patrice Ceballos, Aude Marie-Cardine, Claire Galambrun, Clément Cholle, Isabelle Clerc Urmes, Nadine Petitpain, Marcelo De Carvalho Bittencourt, Véronique Decot, Loïc Reppel, Alexandra Salmon, Laurence Clement, Danièle Bensoussan
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB)...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28480300/toward-a-rapid-production-of-multivirus-specific-t-cells-targeting-bkv-adenovirus-cmv-and-ebv-from-umbilical-cord-blood
#10
Hema Dave, Min Luo, J W Blaney, Shabnum Patel, Cecilia Barese, Conrad Russell Cruz, Elizabeth J Shpall, Catherine M Bollard, Patrick J Hanley
Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28479349/development-of-the-abbott-realtime-zika-assay-for-the-qualitative-detection-of-zika-virus-rna-from-serum-plasma-urine-and-whole-blood-specimens-using-the-m2000-system
#11
Matthew B Frankel, Kinnari Pandya, Jeffrey Gersch, Sarah Siddiqui, George J Schneider
Zika virus is an arthropod-borne flavivirus that has rapidly developed into a world-wide concern. Discovered in 1947, the virus was relatively obscure until an outbreak occurred in 2007 in the Yap islands and spread eventually to the Americas in 2015. Only 20% of patients infected with Zika virus develop symptoms. However, there can be serious consequences of infection including birth defects in developing fetuses and links to Guillain-Barré syndrome. The swift rise in infections has necessitated the development of diagnostic tests for both the detection of viral RNA and the presence of virus-specific antibodies...
May 4, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28472480/characterizing-the-cellular-immune-response-to-parainfluenza-virus-3
#12
Paibel I Aguayo-Hiraldo, Reuben J Arasaratnam, Ifigeneia Tzannou, Manik Kuvalekar, Premal Lulla, Swati Naik, Caridad A Martinez, Pedro A Piedra, Juan F Vera, Ann M Leen
Parainfluenza virus (PIV) 3 infections are a major cause of morbidity and mortality in immunocompromised individuals with no approved therapies. Our group has demonstrated the safety and efficacy of adoptively transferred virus-specific T cells for the prevention and treatment of a broad range of viral infections including BK virus, cytomegalovirus, adenovirus, human herpesvirus 6 and Epstein-Barr virus. However, this approach is restricted to well-characterized viruses with known immunogenic/protective T cell target antigens, precluding extension to PIV-3...
May 2, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28472089/performance-characteristics-of-an-antibody-based-multiplex-kit-for-determining-recent-hiv-1-infection
#13
Kelly A Curtis, Debra L Hanson, Krystin Ambrose Price, S Michele Owen
The availability of reliable laboratory methods for determining recent HIV infection is vital for accurate estimation of population-based incidence. The mean duration of recent infection (MDRI) and false recent rate (FRR) are critical parameters for HIV incidence assays, as they impact HIV incidence estimates and provide a measure of assay performance. The HIV-1 Multiplex assay is an in-house developed, magnetic bead-based assay that measures virus-specific antibody levels and avidity to multiple analytes. To ensure quality control and to facilitate transfer of the assay to external laboratories or testing facilities, the in-house assay has been adapted and produced in kit form...
2017: PloS One
https://www.readbyqxmd.com/read/28468889/hypervariable-domain-of-eastern-equine-encephalitis-virus-nsp3-redundantly-utilizes-multiple-cellular-proteins-for-replication-complex-assembly
#14
Ilya Frolov, Dal Young Kim, Maryna Akhrymuk, James A Mobley, Elena I Frolova
Eastern equine encephalitis virus (EEEV) is a representative member of the New World alphaviruses. It is pathogenic for a variety of vertebrate hosts, in which EEEV induces highly debilitating disease with frequent lethal outcome. Despite a significant public health threat, the molecular mechanism of EEEV replication and interaction with hosts is poorly understood. Our previously published data and those of other teams have demonstrated that hypervariable domains (HVDs) of alphavirus nsP3 protein interact with virus-specific host factors and play critical roles in assembly of viral replication complexes (vRCs)...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28468884/antibody-preparations-from-human-transchromosomic-cows-exhibit-prophylactic-and-therapeutic-efficacy-versus-venezuelan-equine-encephalitis-virus
#15
Christina L Gardner, Chengqun Sun, Thomas Luke, Kanakatte Raviprakash, Hua Wu, Jin-An Jiao, Eddie Sullivan, Douglas S Reed, Kate D Ryman, William B Klimstra
Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus that causes low mortality but high morbidity in humans. In addition to natural outbreaks, there is potential for exposure to VEEV via aerosolized virus particles. There are currently no FDA-licensed vaccines or antiviral therapies for VEEV. Passive immunotherapy is an approved method used to treat individuals against several pathogens and toxins. Human polyclonal antibodies (pAbs) are ideal, but this is dependent upon serum from convalescent human donors, which is in limited supply...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28468011/overcoming-cd8-t-cell-exhaustion-in-viral-hepatitis-lessons-from-the-mouse-model-and-clinical-perspectives
#16
Dominik Wieland, Maike Hofmann, Robert Thimme
About 500 million people all over the world are chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and are thus at high risk of developing liver fibrosis, cirrhosis or hepatocellular carcinoma. While in adults about 90% of acutely HBV-infected patients clear the virus, only 30% of acute HCV infections clear spontaneously. Several mechanisms contribute to the failure in viral clearance. The main factors responsible for the chronification of HBV and HCV infection are, on the one hand, viral escape mutations leading to lack of recognition by antiviral immune cells and, on the other hand, loss of antiviral effector functions of virus-specific CD8+ T cells, called T-cell exhaustion...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28467900/label-free-analysis-of-cd8-t-cell-subset-proteomes-supports-a-progressive-differentiation-model-of-human-virus-specific-t-cells
#17
Michiel C van Aalderen, Maartje van den Biggelaar, Ester B M Remmerswaal, Floris P J van Alphen, Alexander B Meijer, Ineke J M Ten Berge, René A W van Lier
Pathogens trigger T cells to express distinct sets of effector proteins. To better understand the molecular mechanisms that drive functional specification, we used high-resolution mass spectrometry and label-free protein quantification to measure proteomic differences between the seven largest circulating human CD8(+) T cell subsets. Hierarchical clustering of the proteomes placed naive and CD45RA-expressing effector-type T cells at the extremes of the spectrum, with central memory and other effector memory stages located in between...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28466857/tcf1-hepatitis-c-virus-specific-cd8-t-cells-are-maintained-after-cessation-of-chronic-antigen-stimulation
#18
Dominik Wieland, Janine Kemming, Anita Schuch, Florian Emmerich, Percy Knolle, Christoph Neumann-Haefelin, Werner Held, Dietmar Zehn, Maike Hofmann, Robert Thimme
Differentiation and fate of virus-specific CD8(+) T cells after cessation of chronic antigen stimulation is unclear. Here we show that a TCF1(+)CD127(+)PD1(+) hepatitis C virus (HCV)-specific CD8(+) T-cell subset exists in chronically infected patients with phenotypic features of T-cell exhaustion and memory, both before and after treatment with direct acting antiviral (DAA) agents. This subset is maintained during, and for a long duration after, HCV elimination. After antigen re-challenge the less differentiated TCF1(+)CD127(+)PD1(+) population expands, which is accompanied by emergence of terminally exhausted TCF1-CD127-PD1(hi) HCV-specific CD8(+) T cells...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28461487/nasal-associated-lymphoid-tissues-nalts-support-the-recall-but-not-priming-of-influenza-virus-specific-cytotoxic-t-cells
#19
Angela Pizzolla, Zhongfang Wang, Joanna R Groom, Katherine Kedzierska, Andrew G Brooks, Patrick C Reading, Linda M Wakim
The lymphoid tissue that drains the upper respiratory tract represents an important induction site for cytotoxic T lymphocyte (CTL) immunity to airborne pathogens and intranasal vaccines. Here, we investigated the role of the nasal-associated lymphoid tissues (NALTs), which are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage, in the initial priming and recall expansion of CD8(+) T cells following an upper respiratory tract infection with a pathogenic influenza virus and immunization with a live attenuated influenza virus vaccine...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28450868/hepatitis-b-virus-immunopathology-model-systems-and-current-therapies
#20
REVIEW
Praneet Sandhu, Mohammad Haque, Tessa Humphries-Bickley, Swetha Ravi, Jianxun Song
Most people develop acute hepatitis B virus (HBV)-related hepatitis that is controlled by both humoral and cellular immune responses following acute infection. However, a number of individuals in HBV-endemic areas fail to resolve the infection and consequently become chronic carriers. While a vaccine is available and new antiviral drugs are being developed, elimination of persistently infected cells is still a major issue. Standard treatment in HBV infection includes IFN-α, nucleoside, or nucleotide analogs, which has direct antiviral activity and immune modulatory capacities...
2017: Frontiers in Immunology
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