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Chronic viral infection

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https://www.readbyqxmd.com/read/28445592/polo-like-kinase-1-is-a-proviral-host-factor-for-hepatitis-b-virus-replication
#1
Ahmed M Diab, Adrien Foca, Floriane Fusil, Thomas Lahlali, Pascal Jalaguier, Fouzia Amirache, Lia N'Guyen, Nathalie Isorce, François-Loïc Cosset, Fabien Zoulim, Ourania M Andrisani, David Durantel
Chronic Hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for CHB and HCC are perfectible. Herein, we identified cellular Serine/Threonine Polo-like-kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy. To this end, we employed physiologically relevant HBV infection models of Primary Human Hepatocytes (PHH) and differentiated HepaRG cells, in conjunction with pharmacologic PLK1 inhibitors, siRNA-mediated knockdown, and overexpression of constitutively active PLK1 (PLK1(CA) )...
April 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28443809/-twenty-years-of-combination-antiretroviral-therapy-for-hiv-infection-in-the-netherlands-progression-and-new-challenges
#2
K Brinkman, T S Boender, M van der Valk, A van Sighem, P Reiss, F P Kroon
Due to the introduction of combination antiretroviral therapy (cART) 20 years ago, HIV infection in the Netherlands has changed from a fatal disease to a chronic condition with a near normalized life expectancy. The average age of HIV-positive patients continues to increase, as does the prevalence of non-HIV-related comorbidity. The number of new HIV diagnoses seems to be decreasing in the Netherlands, which is partly due to increased testing, earlier diagnosis, prompt cART initiation, and achievement of high levels of viral suppression, resulting in a reduced likelihood of onward transmission...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28442794/innate-and-adaptive-immunity-shape-circulating-hcv-strains
#3
Silvana Gaudieri, Michaela Lucas
An unbiased genome-to-genome analysis in chronic hepatitis C virus (HCV) infection confirms the innate and adaptive arms of the immune system as drivers of viral evolution. Viral adaptation has a critical role in the interaction between host and pathogen and has important clinical implications for infection outcome.
April 26, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28442604/hepatitis-c-virus-indirectly-disrupts-dna-damage-induced-p53-responses-by-activating-protein-kinase-r
#4
Jonathan K Mitchell, Bentley R Midkiff, Benjamin Israelow, Matthew J Evans, Robert E Lanford, Christopher M Walker, Stanley M Lemon, David R McGivern
Many DNA tumor viruses promote cellular transformation by inactivating the critically important tumor suppressor protein p53. In contrast, it is not known whether p53 function is disrupted by hepatitis C virus (HCV), a unique, oncogenic RNA virus that is the leading infectious cause of liver cancer in many regions of the world. Here we show that HCV-permissive, liver-derived HepG2 cells engineered to constitutively express microRNA-122 (HepG2/miR-122 cells) have normal p53-mediated responses to DNA damage and that HCV replication in these cells potently suppresses p53 responses to etoposide, an inducer of DNA damage, or nutlin-3, an inhibitor of p53 degradation pathways...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28440785/impacts-of-hbv-rth55r-polymerase-substitution-on-viral-replication-and-rtm204i-v-resistance-to-nucleoside-nucleotide-antiviral-drugs
#5
Kuan-Hui Xiang, Cheng-Yu Zhao, Shuai Wang, Yao Li, Ming-Ze Su, Qiang-Yi Wang, Xi-Zhan Xu, Juan Deng, Hui Zhuang, Tong Li
BACKGROUND: High genetic variability at reverse transcriptase (RT) region of hepatitis B virus (HBV) could confer resistance to nucleos(t)ide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUCs resistance. METHODS: HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analyzed to identify potential RT substitutions related to NUCs resistance. In vitro studies without and with NUCs were performed in HepG2 cell line transfected by clones with RT harboring wild-type or substituted AA(s) of interest...
April 25, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28440692/both-hepatitis-c-virus-specific-t-cell-responses-and-il28b-rs12979860-single-nucleotide-polymorphism-genotype-influence-antihepatitis-c-virus-treatment-outcome-in-patients-with-chronic-hepatitis-c
#6
José M Benito, Javier García-Samaniego, Marcial García, Antonio Madejón, Luz Martín-Carbonero, Alfonso Cabello, Beatriz Álvarez, Miguel Górgolas, Norma Rallón
Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy...
April 25, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28438690/maturation-of-secreted-hcv-particles-by-incorporation-of-secreted-apoe-protects-from-antibodies-by-enhancing-infectivity
#7
Dorothea Bankwitz, Mandy Doepke, Kathrin Hueging, Romy Weller, Janina Bruening, Patrick Behrendt, Ji-Young Lee, Florian W R Vondran, Michael P Manns, Ralf Bartenschlager, Thomas Pietschmann
BACKGROUND & AIMS: Hepatitis C virus (HCV) evades humoral immunity and establishes chronic infections. Virus particles circulate in complex with lipoproteins facilitating antibody escape. Apolipoprotein E (ApoE) is essential for intracellular HCV assembly and for HCV cell entry. We aimed to explore if ApoE released from non-infected cells interacts with and modulates secreted HCV particles. METHODS: ApoE secreted from non-infected cells was incubated with HCV from primary human hepatocytes or Huh-7...
April 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28437794/hepatitis-b-virus-reactivation-associated-with-direct-acting-antiviral-therapy-for-chronic-hepatitis-c-virus-a-review-of-cases-reported-to-the-u-s-food-and-drug-administration-adverse-event-reporting-system
#8
Susan J Bersoff-Matcha, Kelly Cao, Mihaela Jason, Adebola Ajao, S Christopher Jones, Tamra Meyer, Allen Brinker
Background: Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV-HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis. Objective: To assess whether HBV-R is a safety concern in patients receiving HCV DAAs...
April 25, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28437703/antiviral-treatment-strategies-based-on-gene-silencing-and-genome-editing
#9
REVIEW
Roger Badia, Ester Ballana, José A Esté, Eva Riveira-Muñoz
The ability of some viruses to establish latently infected chronic reservoirs that escape to immune control becomes a major roadblock that impedes the cure of these infections. Therefore, new alternatives are needed to pursuit the eradication of viral persistent infections. Gene silencing technologies are in constant evolution and provide an outstanding sequence specificity that allows targeting any coding sequence of interest. Here we provide an overview of the development of gene silencing technologies ranging from initially RNA interference to the recently developed CRISPR/Cas9 and their potential as new antiviral strategies focusing on the eradication of HIV...
April 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28437539/safety-and-efficacy-of-antiviral-therapy-for-prevention-of-cytomegalovirus-reactivation-in-immunocompetent-critically-ill-patients-a-randomized-clinical-trial
#10
Nicholas J Cowley, Andrew Owen, Sarah C Shiels, Joanne Millar, Rebecca Woolley, Natalie Ives, Husam Osman, Paul Moss, Julian F Bion
Importance: Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness. Objective: To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients. Design, Setting, and Participants: A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014...
April 24, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28436552/systematic-review-with-meta-analysis-the-efficacy-and-safety-of-tenofovir-to-prevent-mother-to-child-transmission-of-hepatitis-b-virus
#11
REVIEW
M H Hyun, Y-S Lee, J H Kim, J H Je, Y J Yoo, J E Yeon, K S Byun
BACKGROUND: Preventing mother to child transmission of chronic hepatitis B infection in the setting of a high maternal viral load is challenging. The idea has emerged from antepartum tenofovir treatment with combination immunoprophylaxis. AIMS: To demonstrate the efficacy and safety of tenofovir to prevent mother to child transmission of hepatitis B virus. METHODS: PubMed, EMBASE, and Cochrane databases were searched through August 16, 2016...
April 24, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28434648/nivolumab-in-patients-with-advanced-hepatocellular-carcinoma-checkmate-040-an-open-label-non-comparative-phase-1-2-dose-escalation-and-expansion-trial
#12
Anthony B El-Khoueiry, Bruno Sangro, Thomas Yau, Todd S Crocenzi, Masatoshi Kudo, Chiun Hsu, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore H Welling, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Dela Cruz, Lixin Lang, Jaclyn Neely, Hao Tang, Homa B Dastani, Ignacio Melero
BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. METHODS: We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection...
April 20, 2017: Lancet
https://www.readbyqxmd.com/read/28433762/novel-viral-and-host-targets-to-cure-hepatitis-b
#13
REVIEW
Chunkyu Ko, Thomas Michler, Ulrike Protzer
Hepatitis B virus (HBV) infection is a global health threat with 240 million chronic carriers at high risk to develop hepatocellular carcinoma. Current antiviral treatment can efficiently control viral replication and reduce liver inflammation, but is still quite far from achieving a cure. Significant progress has been made in understanding the virus life cycle and virus-host interaction in the past few years. With identification of the HBV receptor, cell-culture infection systems have become available that allow drug screening and establishing a pipeline of potential antivirals targeting either viral or host factors...
April 20, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28432209/a-prospective-observational-cohort-study-of-the-seasonal-dynamics-of-airway-pathogens-in-the-aetiology-of-exacerbations-in-copd
#14
Tom M A Wilkinson, Emmanuel Aris, Simon Bourne, Stuart C Clarke, Mathieu Peeters, Thierry G Pascal, Sonia Schoonbroodt, Andrew C Tuck, Viktoriya Kim, Kristoffer Ostridge, Karl J Staples, Nicholas Williams, Anthony Williams, Stephen Wootton, Jeanne-Marie Devaster
BACKGROUND: The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood. Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events. METHODS: In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses. Results are presented for subjects in the full cohort, followed for 1 year...
April 21, 2017: Thorax
https://www.readbyqxmd.com/read/28428210/proton-chemical-shift-imaging-study-of-the-combined-antiretroviral-therapy-impact-on-neurometabolic-parameters-in-chronic-hiv-infection
#15
J Boban, D Kozic, V Turkulov, D Lendak, M Bjelan, M Semnic, S Brkic
BACKGROUND AND PURPOSE: The introduction of combination antiretroviral therapy has failed to reduce the high prevalence of mild forms of HIV-associated neurocognitive disorders. The aim of this study was to test the effect of combined antiretroviral therapy on brain metabolite ratios in chronic HIV infection by using proton chemical shift imaging. MATERIALS AND METHODS: We performed 2D chemical shift imaging in 91 subjects (31 HIV+ patients with chronic infection on combination antiretroviral therapy, 19 combination antiretroviral therapy-na|fkve HIV+ subjects with chronic infection, and 41 healthy controls), covering frontal and parietal subcortical white and cingulate gyrus gray matter, analyzing ratios of NAA/Cr and Cho/Cr on long-TE and mIns/Cr on short-TE MR spectroscopy...
April 20, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28427875/easl-2017-clinical-practice-guidelines-on-the-management-of-hepatitis-b-virus-infection
#16
Pietro Lampertico, Kosh Agarwal, Thomas Berg, Maria Buti, Harry L A Janssen, George Papatheodoridis, Fabien Zoulim, Frank Tacke
Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors including vaccination policies and migration. This Clinical Practice Guideline presents updated recommendations for the optimal management of HBV infection. Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis and (V) HBsAg-negative phase...
April 18, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28426876/genome-wide-dna-methylation-analysis-during-non-alcoholic-steatohepatitis-related-multistage-hepatocarcinogenesis-comparison-with-hepatitis-virus-related-carcinogenesis
#17
Junko Kuramoto, Eri Arai, Ying Tian, Nobuaki Funahashi, Masaki Hiramoto, Takao Nammo, Yuichi Nozaki, Yoriko Takahashi, Nanako Ito, Ayako Shibuya, Hidenori Ojima, Aoi Sukeda, Yosuke Seki, Kazunori Kasama, Kazuki Yasuda, Yae Kanai
The aim of this study was to clarify the significance of DNA methylation alterations during non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Single-CpG-resolution genome-wide DNA methylation analysis was performed on 264 liver tissue samples using the Illumina Infinium HumanMethylation450 BeadChip. After Bonferroni correction, 3331 probes showed significant DNA methylation alterations in 113 samples of non-cancerous liver tissue showing NASH (NASH-N) as compared with 55 samples of normal liver tissue (NLT)...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28425927/hepatitis-e-virus-genotypes-and-evolution-emergence-of-camel-hepatitis-e-variants
#18
REVIEW
Siddharth Sridhar, Jade L L Teng, Tsz-Ho Chiu, Susanna K P Lau, Patrick C Y Woo
Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. Zoonotic HEV is an important cause of chronic hepatitis in immunocompromised patients. The rapid identification of novel HEV variants and accumulating sequence information has prompted significant changes in taxonomy of the family Hepeviridae. This family includes two genera: Orthohepevirus, which infects terrestrial vertebrates, and Piscihepevirus, which infects fish. Within Orthohepevirus, there are four species, A-D, with widely differing host range...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28425257/role-of-hygienic-factors-in-the-etiology-of-allergic-disorders-in-children
#19
Şule Yeşil, Ahmet Kan, Olkar Abdulmajed, Arzu Bakirtaş, Nedim Sultan, Sadık M Demirsoy
BACKGROUND/AIM: We investigated the role of body flora and chronic inflammatory infections in the etiology of allergic disorders in Turkish children. MATERIALS AND METHODS: Forty pediatric asthma patients with positive skin prick tests and 40 age-matched healthy subjects with negative skin prick tests were enrolled in this cross-sectional study. Serum H. pylori IgG, viral hepatitis serology, IL-10, and TGF-beta levels were measured. Stool and throat cultures were taken and tested for occurrence of microorganisms...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28424687/cd103-cd8-t-cells-in-the-toxoplasma-infected-brain-exhibit-a-tissue-resident-memory-transcriptional-profile
#20
Tyler A Landrith, Suhas Sureshchandra, Andrea Rivera, Jessica C Jang, Maham Rais, Meera G Nair, Ilhem Messaoudi, Emma H Wilson
During chronic infection, memory T cells acquire a unique phenotype and become dependent on different survival signals than those needed for memory T cells generated during an acute infection. The distinction between the role of effector and memory T cells in an environment of persistent antigen remains unclear. Here, in the context of chronic Toxoplasma gondii infection, we demonstrate that a population of CD8 T cells exhibiting a tissue-resident memory (TRM) phenotype accumulates within the brain. We show that this population is distributed throughout the brain in both parenchymal and extraparenchymal spaces...
2017: Frontiers in Immunology
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