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https://www.readbyqxmd.com/read/29145453/the-antiviral-drug-tenofovir-an-inhibitor-of-pannexin-1-mediated-atp-release-prevents-liver-and-skin-fibrosis-by-downregulating-adenosine-levels-in-the-liver-and-skin
#1
Jessica L Feig, Aranzazu Mediero, Carmen Corciulo, Hailing Liu, Jin Zhang, Miguel Perez-Aso, Laura Picard, Tuere Wilder, Bruce Cronstein
BACKGROUND: Fibrosing diseases are a leading cause of morbidity and mortality worldwide and, therefore, there is a need for safe and effective antifibrotic therapies. Adenosine, generated extracellularly by the dephosphorylation of adenine nucleotides, ligates specific receptors which play a critical role in development of hepatic and dermal fibrosis. Results of recent clinical trials indicate that tenofovir, a widely used antiviral agent, reverses hepatic fibrosis/cirrhosis in patients with chronic hepatitis B infection...
2017: PloS One
https://www.readbyqxmd.com/read/29145306/dynamic-noninvasive-markers-predict-hepatocellular-carcinoma-in-chronic-hepatitis-c-patients-without-sustained-virological-response-after-interferon-based-therapy-prioritize-who-needs-urgent-direct-acting-antiviral-agents
#2
Chao-Min Huang, Tsung-Hui Hu, Kuo-Chin Chang, Po-Lin Tseng, Sheng-Nan Lu, Chien-Hung Chen, Jing-Houng Wang, Chuan-Mo Lee, Ming-Chao Tsai, Ming-Tsung Lin, Yi-Hao Yen, Chao-Hung Hung, Chung-Lung Cho, Cheng-Kun Wu
Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29144593/risk-factors-for-seasonal-influenza-virus-detection-in-stools-of-patients-consulting-in-general-practice-for-acute-respiratory-infections-in-france-2014-2016
#3
L Minodier, S Masse, L Capai, T Blanchon, P E Ceccaldi, S van der Werf, T Hanslik, N R Charrel, A Falchi
BACKGROUND: Previous studies reported detection of influenza RNA in stools of patients with seasonal influenza infection. While this detection may have a clinical significance, other factors may influence the stools positivity for influenza viruses. OBJECTIVES: The objective of this study was to investigate demographical, clinical and microbiological factors which could favour the presence of influenza viral RNA in the stools of patients with laboratory-confirmed influenza infection...
November 16, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/29144498/corrigendum-the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#4
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
This corrects the article DOI: 10.1038/ni.3830.
November 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29143896/modulation-of-stimulator-of-interferon-genes-sting-expression-by-interferon-%C3%AE-in-human-keratinocytes
#5
Yohei Nishikawa, Yasushi Matsuzaki, Kazuyuki Kimura, Akiko Rokunohe, Hajime Nakano, Daisuke Sawamura
Infection of microbial pathogen triggers the innate immune system, and the induction of interferons (IFNs) play a vital role in host antiviral response. Stimulator of interferon genes (STING) was identified as a crucial regulator of the DNA sensing pathway, and activates both nuclear factor-κB and interferon regulatory factor 3 transcription pathways to evoke IFNs production. In this study, we studied the upregulation of STING mRNA expression, induced by IFN-γ in human keratinocytes (HaCaT). STING promoter assays clarified that a gamma-activated sequence (GAS), located at - 7 to - 15-bp, is required for IFN-γ-upregulated promoter activity...
November 16, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/29143681/economic-evaluation-of-hcv-testing-approaches-in-low-and-middle-income-countries
#6
REVIEW
Jake R Morgan, Maria Servidone, Philippa Easterbrook, Benjamin P Linas
BACKGROUND: Hepatitis C virus (HCV) infection represents a major public health burden with diverse epidemics worldwide, but at present, only a minority of infected persons have been tested and are aware of their diagnosis. The advent of highly effective direct acting antiviral (DAA) therapy, which is becoming available at increasingly lower costs in low and middle income countries (LMICs), represents a major opportunity to expand access to testing and treatment. However, there is uncertainty as to the optimal testing approaches and who to prioritize for testing...
November 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29143675/economic-evaluations-of-hbv-testing-and-treatment-strategies-and-applicability-to-low-and-middle-income-countries
#7
REVIEW
Shevanthi Nayagam, Elisa Sicuri, Maud Lemoine, Philippa Easterbrook, Lesong Conteh, Timothy B Hallett, Mark Thursz
BACKGROUND: Many people living with chronic HBV infection remain undiagnosed until later stages of disease. Increasing testing and treatment rates form part of the strategy to respond to the WHO goal of eliminating viral hepatitis as a public health threat by 2030. However, achieving these ambitious targets is dependent on finding effective and cost-effective methods of scale up strategies. The aim of this study was to undertake a narrative review of the literature on economic evaluations of testing and treatment for HBV infection, to help inform the development of the 2017 WHO Hepatitis Testing Guidelines...
November 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29143615/diagnostic-accuracy-of-tests-to-detect-hepatitis-c-antibody-a-meta-analysis-and-review-of-the-literature
#8
Weiming Tang, Wen Chen, Ali Amini, Debi Boeras, Jane Falconer, Helen Kelly, Rosanna Peeling, Olivia Varsaneux, Joseph D Tucker, Philippa Easterbrook
BACKGROUND: Although direct-acting antivirals can achieve sustained virological response rates greater than 90% in Hepatitis C Virus (HCV) infected persons, at present the majority of HCV-infected individuals remain undiagnosed and therefore untreated. While there are a wide range of HCV serological tests available, there is a lack of formal assessment of their diagnostic performance. We undertook a systematic review and meta-analysis to evaluate he diagnostic accuracy of available rapid diagnostic tests (RDT) and laboratory based EIA assays in detecting antibodies to HCV...
November 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29143611/one-or-two-serological-assay-testing-strategy-for-diagnosis-of-hbv-and-hcv-infection-the-use-of-predictive-modelling
#9
John V Parry, Philippa Easterbrook, Anita R Sands
BACKGROUND: Initial serological testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is conducted using either rapid diagnostic tests (RDT) or laboratory-based enzyme immunoassays (EIA)s for detection of hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV), typically on serum or plasma specimens and, for certain RDTs, capillary whole blood. WHO recommends the use of standardized testing strategies - defined as a sequence of one or more assays to maximize testing accuracy while simplifying the testing process and ideally minimizing cost...
November 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29143192/middle-east-respiratory-syndrome-and-severe-acute-respiratory-syndrome-current-therapeutic-options-and-potential-targets-for-novel-therapies
#10
REVIEW
Julie Dyall, Robin Gross, Jason Kindrachuk, Reed F Johnson, Gene G Olinger, Lisa E Hensley, Matthew B Frieman, Peter B Jahrling
No specific antivirals are currently available for two emerging infectious diseases, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). A literature search was performed covering pathogenesis, clinical features and therapeutics, clinically developed drugs for repurposing and novel drug targets. This review presents current knowledge on the epidemiology, pathogenesis and clinical features of the SARS and MERS coronaviruses. The rationale for and outcomes with treatments used for SARS and MERS is discussed...
November 15, 2017: Drugs
https://www.readbyqxmd.com/read/29142571/in-vitro-transcription-analysis-of-ns5a-from-hcv-3a-circulating-in-pakistani-patients-with-chronic-hepatitis-c-and-their-differential-response-to-antiviral-therapy
#11
Shameem Bhatti, Sobia Manzoor, Fahed Parvaiz, Javed Ashraf, Farakh Javed
Objective: Mutations in HCV nonstructural protein 5A (NS5A) play a vital role in virus resistance. The aim of this study was to develop a correlation between NS5A mutations (genotype 3a) and virological response towards interferon alpha (IFN-α) plus ribavirin therapy. Methods: In this study, which was conducted from 09-02-2013 to 25-11-2015 in the rural area of Province Sindh - Pakistan, total patients' responses to peg-IFN therapy were investigated. Patients were given peg-IFN therapy for 24 to 48 weeks and categorized as sustained virologic responders (SVR) or non-responders (NR) to HCV infection...
September 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/29142134/tnf-mediated-survival-of-cd169-cells-promotes-immune-activation-during-vesicular-stomatitis-virus-infection
#12
Prashant V Shinde, Haifeng C Xu, Sathish Kumar Maney, Andreas Kloetgen, Sukumar Namineni, Yuan Zhuang, Nadine Honke, Namir Shaabani, Nicolas Bellora, Mareike Doerrenberg, Mirko Trilling, Vitaly I Pozdeev, Nico van Rooijen, Stefanie Scheu, Klaus Pfeffer, Paul R Crocker, Masato Tanaka, Sujitha Duggimpudi, Percy Knolle, Mathias Heikenwalder, Jürgen Ruland, Tak W Mak, Dirk Brenner, Aleksandra A Pandyra, Jessica I Hoell, Arndt Borkhardt, Dieter Häussinger, Karl S Lang, Philipp A Lang
Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain unclear. Here we show that tumor necrosis factor is produced by CD11b(+) Ly6C(+)Ly6G(+) cells following infection with VSV. The absence of TNF or TNF receptor 1 (TNFR1) resulted in reduced numbers of CD169(+) cells and in reduced IFN-I production during VSV infection, with a severe disease outcome...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142133/human-adenovirus-infection-causes-the-cellular-mkrn1-e3-ubiquitin-ligase-degradation-involving-the-viral-core-protein-pvii
#13
Raviteja Inturi, Kwangchol Mun, Katrin Singethan, Sabrina Schreiner, Tanel Punga
Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII interacting protein in HAdV-C5-infected cells...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142132/identification-of-a-small-molecule-that-compromises-the-structural-integrity-of-viroplasms-and-rotavirus-double-layered-particles
#14
Catherine Eichwald, Giuditta De Lorenzo, Elisabeth M Schraner, Guido Papa, Michela Bollati, Paolo Swuec, Matteo de Rosa, Mario Milani, Eloise Mastrangelo, Mathias Ackermann, Oscar R Burrone, Francesca Arnoldi
Despite the availability of two attenuated vaccines, rotavirus (RV) gastroenteritis remains an important cause of mortality among children in developing countries causing about 215,000 infant deaths annually. Currently, there are no specific antiviral therapies available. RV is a non-enveloped virus with a segmented double-stranded RNA genome. Viral genome replication and assembly of transcriptionally active double-layered particles (DLPs) take place in cytoplasmic viral structures called viroplasms. In this study, we describe strong impairment of the early stages of RV replication induced by a small molecule known as RNA polymerase III inhibitor, ML-60218 (ML)...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142128/interaction-between-a-unique-minor-protein-and-a-major-capsid-protein-of-bluetongue-virus-controls-virus-infectivity
#15
Eiko Matsuo, Kiyoshi Yamazaki, Hiroki Tsuruta, Polly Roy
Among the Reoviridae family of double-stranded RNA viruses, only members of the Orbivirus genus possess a unique structural protein, termed VP6, within their particles. Bluetongue virus (BTV), an important livestock pathogen, is the prototype Orbivirus The BTV VP6 is an ATP-dependent RNA helicase and it is indispensable for virus replication. In this report, we investigated how VP6 might be recruited to the virus capsid and whether the BTV structural protein VP3, which forms the internal layer of the virus capsid core, is involved in VP6 recruitment...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29141870/ig%C3%AE-ubiquitination-activates-pi3k-signals-required-for-endosomal-sorting
#16
Margaret Veselits, Azusa Tanaka, Yaoqing Chen, Keith Hamel, Malay Mandal, Matheswaran Kandasamy, Balaji Manicassamy, Shannon K O'Neill, Patrick Wilson, Roger Sciammas, Marcus R Clark
A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC)...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141777/design-synthesis-and-biological-evaluation-of-novel-oseltamivir-derivatives-as-potent-neuraminidase-inhibitors
#17
Zhen Wang, Li Ping Cheng, Xing Hua Zhang, Wan Pang, Liang Li, Jin Long Zhao
Neuraminidase (NA) is one of the particular potential targets for novel antiviral therapy. In this work, a series of neuraminidase inhibitors with the cyclohexene scaffold were studied based upon the combination of 3D-QSAR, molecular docking, and molecular dynamics techniques. The results indicate that the built 3D-QSAR models yield reliable statistical information: the correlation coefficient (r(2)) and cross-validation coefficient (q(2)) of CoMFA (comparative molecular field analysis) are 0.992 and 0.819; the r(2) and q(2) of CoMSIA (comparative molecular similarity analysis) are 0...
November 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29141351/-qidong-chronic-hepatitis-b-cohort-participants-enrollment-and-comparison-of-baseline-characteristics-by-gender-stratification
#18
F Liang, C X Sha, C S Fan, W G Chen, H Tu, F Yang, G W Cao, H S Qin
Objective: To establish a study cohort of chronic hepatitis B (CHB) in Qidong and evaluate its baseline characteristics. Methods: CHB outpatients of the Third People's Hospital of Qidong were invited to participate in baseline survey from January 1, 2016, including questionnaire survey, liver function detection, serum detection of HBV infection and upper abdomen ultrasound detection. Anticipated sample size was at least one thousand. Baseline data were inputted by EpiData 3.1 software and then cleaned and analyzed by SAS 9...
November 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/29141265/-hbv-infections-in-germany-health-care-costs-in-a-real-life-setting
#19
Jona Theodor Stahmeyer, Hans Becker, Anna Lena Orlemann, Christian Krauth, Michael P Manns, Heiner Wedemeyer
Background An estimated 500 000 people are infected with hepatitis B in Germany, inducing an enormous burden on infected patients and the health care system. The aim of our study was to estimate the real-life costs of treating hepatitis B and to analyze sociodemographic factors. Methods We conducted a retrospective, non-interventional, single-center study from 07/2009 to 12/2012. Information on health care delivery was extracted from patient records. Besides that, a questionnaire survey regarding sociodemographic parameters and quality of life of HBV-infected patients was performed...
November 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/29141246/evaluation-of-temporal-virological-responses-to-interferon-%C3%AE-2b-plus-ribavirin-among-genotype-3a-hepatitis-c-virus-infected-patients
#20
Abida Raza, Muhammad Ovais, Hafsa Aziz, Asim Anwar, Javaid Irfan, Irshad Ahmad, Muhammad Mukhtar
OBJECTIVES: The present study aimed to examine the impact of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in chronic hepatitis C genotype 3a individuals. METHODS: The patients were given antiviral therapy with IFN-α-2b, 3 million units 3 times a week and 800-1,200 mg of ribavirin daily adjusted to the patient's body weight (<60 kg 800 mg day-1, and >60 kg 1,200 day-1). The patients received this combination therapy for 24 weeks...
November 16, 2017: Intervirology
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