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Immune response to HCV

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https://www.readbyqxmd.com/read/27910749/role-of-toll-like-receptors-in-hepatitis-c-virus-pathogenesis-and-treatment
#1
Usman Ali Ashfaq, Muhammad Sarfaraz Iqbal, Saba Khaliq
Viral infections are rising every day, and viruses appear to be the most dangerous pathogens in the world. Hepatitis C virus (HCV) is accepted as one of the major destructive factors of promoting severe hepatic disorders by infecting more than 180 million individuals throughout the world. Chronic infection caused by HCV poses a serious global health emergency and appears to be a powerful threat to humanity. Almost 20 years have passed since the disclosure of HCV, but even now, treatment preferences remain limited...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27902444/oncolytic-reovirus-as-a-combined-antiviral-and-anti-tumour-agent-for-the-treatment-of-liver-cancer
#2
Adel Samson, Matthew J Bentham, Karen Scott, Gerard Nuovo, Abigail Bloy, Elizabeth Appleton, Robert A Adair, Rajiv Dave, Adam Peckham-Cooper, Giles Toogood, Seishi Nagamori, Matthew Coffey, Richard Vile, Kevin Harrington, Peter Selby, Fiona Errington-Mais, Alan Melcher, Stephen Griffin
OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. DESIGN AND RESULTS: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication...
November 15, 2016: Gut
https://www.readbyqxmd.com/read/27902328/hepatitis-c-virus-core-activates-proteasomal-activator-28-gamma-expression-via-upregulation-of-p53-levels-to-control-virus-propagation
#3
Juri Kwak, Indira Tiwari, Kyung Lib Jang
The proteasomal activator PA28γ, frequently overexpressed in hepatocellular carcinoma (HCC), is believed to play several important roles in hepatitis C virus (HCV) replication and viral pathogenesis. However, the underlying mechanism for PA28γ overexpression in HCC and its role during HCV replication are still unclear. In the present study, we found that HCV Core derived from either ectopic expression or HCV infection upregulates PA28γ levels in p53-positive human hepatocytes. For this effect, HCV Core sequentially activated ataxia telangiectasia mutated and checkpoint kinase 2 via phosphorylation at Ser-1981 and Thr-68 residues, respectively, resulting in stabilization of p53 via phosphorylation at Ser-15 and Ser-20 residues and subsequent transcriptional activation of PA28γ expression...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902325/targeting-naturally-occurring-epitope-variants-of-hepatitis-c-virus-with-high-affinity-t-cell-receptors
#4
Huajun Zhang, Jianbing Zhang, Lei Chen, Zhiming Weng, Ye Tian, Haifeng Zhao, Youjia Li, Lin Chen, Zhaoduan Liang, Hongjun Zheng, Wenzhuo Zhao, Shi Zhong, Yi Li
Hepatitis C virus (HCV) readily establishes chronic infection, which is characterized by failure of virus-specific CD8+ T cells. HCV uses epitope mutation and T-cell exhaustion to escape from the host immune response. Previously, we engineered high-affinity T-cell receptors (HATs) targeting HIV escape mutants. In this study, the affinity of a T-cell receptor specific for the human leukocyte antigen (HLA)-A2-restricted HCV immunodominant epitope NS3 1406-1415 (KLVALGINAV) was improved from a KD of 6.6 µM to 40 pM...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27888401/the-impact-of-chronic-hepatitis-c-infection-on-cholesterol-metabolism-in-pbmcs-is-associated-with-microrna-146a-expression
#5
M Sidorkiewicz, M Grek, B Jozwiak, A Krol, A Piekarska
Chronic hepatitis C (CHC) infection is known to induce important changes in host cholesterol metabolism. MicroRNAs (miRNAs) regulate the expression of many genes and, in consequence, control various processes, including human metabolism and response to viral infection. Recently, the alteration of the immune-associated miR-146a, which is abundantly present in peripheral blood mononuclear cells (PBMCs), was found in some viral infections. The study aimed to analyse the influence of hepatitis C virus (HCV) infection on miR-146a expression in PBMCs in vivo and in vitro, as well as to assess the possible impact of miR-146a alteration on the intracellular cholesterol level in PBMCs...
November 25, 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27888126/understanding-the-complex-evolution-of-rapidly-mutating-viruses-with-deep-sequencing-beyond-the-analysis-of-viral-diversity
#6
REVIEW
Preston Leung, Auda A Eltahla, Andrew R Lloyd, Rowena A Bull, Fabio Luciani
With the advent of affordable deep sequencing technologies, detection of low frequency variants within genetically diverse viral populations can now be achieved with unprecedented depth and efficiency. The high-resolution data provided by next generation sequencing technologies is currently recognised as the gold standard in estimation of viral diversity. In the analysis of rapidly mutating viruses, longitudinal deep sequencing datasets from viral genomes during individual infection episodes, as well as at the epidemiological level during outbreaks, now allow for more sophisticated analyses such as statistical estimates of the impact of complex mutation patterns on the evolution of the viral populations both within and between hosts...
November 22, 2016: Virus Research
https://www.readbyqxmd.com/read/27888038/evidence-of-bottleneck-effect-on-hepatitis-c-virus-transmission-between-a-couple-under-interferon-based-therapy
#7
Rafael Alves da Silva, Isabel Maria Vicente Guedes de Carvalho, Renata Prandini Adum de Matos, Lilian Hiromi Tomonari Yamasaki, Cíntia Bittar, Paula Rahal, Ana Carolina Gomes Jardim
Issues on the correlation of viral genetic diversity and treatment response to the hepatitis C infection remain uncertain. The bottleneck effect dictates the characteristics of the viral population that will establish the infection in a new host and is related to how the immune system and treatment will be effective against the virus. Here we evaluated the phylogenetic characteristics of quasispecies population and the treatment response pattern of a HCV infected couple. We also analyzed whether the viral population of these patients indicated that they were exposed to the same source for primer infection...
November 22, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27885757/role-of-primary-t-cell-immunodeficiency-and-hepatitis-b-coinfection-on-spontaneous-clearance-of-hepatitis-c-the-bc-hepatitis-testers-cohort
#8
N Islam, M Krajden, M Gilbert, P Gustafson, A Yu, M Kuo, M Chong, M Alvarez, J Wong, M W Tyndall, N Z Janjua
T-cell host immune response against hepatitis C virus (HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T-cell deficiency along with other factors on the spontaneous clearance of HCV in a large population-based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked with data on their medical visits, hospitalizations and prescription drugs...
November 25, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27875997/identification-of-the-transcripts-associated-with-spontaneous-hcv-clearance-in-individuals-co-infected-with-hiv-and-hcv
#9
Yue Chen, Chengli Shen, Debjani Guha, Ming Ding, Scott Kulich, Aiymkul Ashimkhanova, Charles Rinaldo, Eric Seaberg, Joseph B Margolick, Valentina Stosor, Otoniel Martínez-Maza, Phalguni Gupta
BACKGROUND: Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20-46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance...
November 22, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27872681/alcohol-use-disorder-and-its-impact-on-chronic-hepatitis-c-virus-and-human-immunodeficiency-virus-infections
#10
REVIEW
Daniel Fuster, Arantza Sanvisens, Ferran Bolao, Inmaculada Rivas, Jordi Tor, Robert Muga
Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease...
November 8, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27867514/hepatitis-c-virus-drives-the-pathogenesis-of-hepatocellular-carcinoma-from-immune-evasion-to-carcinogenesis
#11
Miriam Canavese, Danushka Wijesundara, Guy J Maddern, Branka Grubor-Bauk, Ehud Hauben
Persistent hepatitis C virus (HCV) infection is associated with high incidence of hepatocellular carcinoma (HCC), the most common primary malignancy of the liver with over half a million new cases diagnosed annually worldwide. The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed transcription factor and its activation by environmental chemicals and by its endogenous ligand kynurenine (Kyn) has been implicated in a variety of tumour-promoting processes such as transformation, tumorigenesis and in immunosuppression that enables tumour survival and growth...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27861593/neutrophil-and-monocyte-function-in-patients-with-chronic-hepatitis-c-undergoing-antiviral-therapy-with-regimens-containing-protease-inhibitors-with-and-without-interferon
#12
Martina Gambato, Noelia Caro-Pérez, Patricia González, Nuria Cañete, Zoe Mariño, Sabela Lens, Martín Bonacci, Concepció Bartres, José-María Sánchez-Tapias, José A Carrión, Xavier Forns, Manel Juan, Sofía Pérez-Del-Pulgar, María-Carlota Londoño
Real-life data showed an increased incidence of bacterial infections in patients with advanced liver disease receiving a protease inhibitor (PI)-containing antiviral regimen against hepatitis C (HCV). However, the causes of this event are unknown. We hypothesized that PIs might impair innate immune responses through the inhibition of proteases participating in the anti-bacterial functions of neutrophils and monocytes. The aims of the study were to assess phagocytic and oxidative burst capacity in neutrophils and monocytes obtained from patients receiving a PI containing-antiviral regimen, and to determine cytokine secretion after neutrophil stimulation with flagellin...
2016: PloS One
https://www.readbyqxmd.com/read/27860532/hepatitis-c-virus-e2-protein-induces-upregulation-of-il-8-pathways-and-production-of-heat-shock-proteins-in-human-thyroid-cells
#13
Sara Salehi Hammerstad, Mihaela Stefan, Jason Blackard, Randall P Owen, Hanna J Lee, Erlinda Concepcion, Zhengzi Yi, Weijia Zhang, Yaron Tomer
CONTEXT: Thyroiditis is one of the most common extra hepatic manifestations of hepatitis C virus infection. By binding to surface cell receptor CD81, hepatitis C envelop glycoprotein E2 mediates entry of HCV into cells. Studies have shown that different viral proteins may individually induce host responses to infection. We hypothesized that HCV E2 protein binding to CD81 expressed on thyroid cells activates a cascade of inflammatory responses that can trigger autoimmune thyroiditis in susceptible individuals...
November 18, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27849172/novel-e2-glycoprotein-tetramer-detects-hepatitis-c-virus-specific-memory-b-cells
#14
Maude Boisvert, Wanrui Zhang, Elizabeth J Elrod, Nicole F Bernard, Jean-Pierre Villeneuve, Julie Bruneau, Joseph Marcotrigiano, Naglaa H Shoukry, Arash Grakoui
Acute hepatitis C virus (HCV) infection culminates in viral persistence in the majority of cases. Abs that recognize the envelope glycoproteins E1 and E2 are generated during the late stages of acute infection, yet their contribution to spontaneous viral clearance remains controversial. Investigation of the humoral responses during acute HCV infection have been limited by the inability to directly identify and characterize HCV-specific B cells. In this study we describe the development of a novel tetramer of the E2 glycoprotein ectodomain (J6, genotype 2a strain), which allowed us to visualize E2-specific B cells longitudinally in the peripheral blood of HCV-infected individuals...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27843539/regulatory-and-activated-effector-t-cells-in-chronic-hepatitis-c-virus-relation-to-autoimmunity
#15
Hanan Fouad, Maissa El Raziky, Eman Medhat Hassan, Ghada Mahmoud Abdel Aziz, Samar K Darweesh, Ahmed Reda Sayed
AIM: To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS: A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group...
October 28, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27834208/expanding-the-host-range-of-hepatitis-c-virus-through-viral-adaptation
#16
Markus von Schaewen, Marcus Dorner, Kathrin Hueging, Lander Foquet, Sherif Gerges, Gabriela Hrebikova, Brigitte Heller, Julia Bitzegeio, Juliane Doerrbecker, Joshua A Horwitz, Gisa Gerold, Sebastian Suerbaum, Charles M Rice, Philip Meuleman, Thomas Pietschmann, Alexander Ploss
: Hepatitis C virus (HCV) species tropism is incompletely understood. We have previously shown that at the level of entry, human CD81 and occludin (OCLN) comprise the minimal set of human factors needed for viral uptake into murine cells. As an alternative approach to genetic humanization, species barriers can be overcome by adapting HCV to use the murine orthologues of these entry factors. We previously generated a murine tropic HCV (mtHCV or Jc1/mCD81) strain harboring three mutations within the viral envelope proteins that allowed productive entry into mouse cell lines...
November 8, 2016: MBio
https://www.readbyqxmd.com/read/27833096/immunoproteasome-induction-is-suppressed-in-hepatitis-c-virus-infected-cells-in-a-protein-kinase-r-dependent-manner
#17
In Soo Oh, Kathrin Textoris-Taube, Pil Soo Sung, Wonseok Kang, Xenia Gorny, Thilo Kähne, Seon-Hui Hong, Young Joon Choi, Clemens Cammann, Michael Naumann, Jong Hoon Kim, Su-Hyung Park, Ook Joon Yoo, Peter M Kloetzel, Ulrike Seifert, Eui-Cheol Shin
By changing the relative abundance of generated antigenic peptides through alterations in the proteolytic activity, interferon (IFN)-γ-induced immunoproteasomes influence the outcome of CD8(+) cytotoxic T lymphocyte responses. In the present study, we investigated the effects of hepatitis C virus (HCV) infection on IFN-γ-induced immunoproteasome expression using a HCV infection cell culture system. We found that, although IFN-γ induced the transcriptional expression of mRNAs encoding the β1i/LMP2, β2i/MECL-1 and β5i/LMP7 immunoproteasome subunits, the formation of immunoproteasomes was significantly suppressed in HCV-infected cells...
November 11, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27830380/recovery-of-pan-genotypic-and-genotype-specific-amino-acid-alterations-in-chronic-hepatitis-c-after-viral-clearance-transition-at-the-crossroad-of-metabolism-and-immunity
#18
Ming-Ling Chang, Mei-Ling Cheng, Su-Wei Chang, Hsiang-Yu Tang, Cheng-Tang Chiu, Chau-Ting Yeh, Ming-Shi Shiao
Recovery of amino acid (AA) metabolism and the associated clinical implications in chronic hepatitis C (CHC) patients with sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remains elusive. A prospective cohort study was conducted on 222 CHC patients with SVR. Eighty-two age-matched male genotype 1 (G1) and G2 patients underwent paired serum metabolomics analyses with liquid chromatography-tandem mass spectrometry to examine AAs before and 24 weeks after anti-HCV therapy. Before anti-HCV therapy, G1 patients had a higher HCV RNA level than G2 patients...
November 10, 2016: Amino Acids
https://www.readbyqxmd.com/read/27816492/tremelimumab-in-combination-with-ablation-in-patients-with-advanced-hepatocellular-carcinoma
#19
Austin G Duffy, Susanna V Ulahannan, Oxana Makorova-Rusher, Osama Rahma, Heiner Wedemeyer, Drew Pratt, Jeremy L Davis, Marybeth S Hughes, Theo Heller, Mei ElGindi, Ashish Uppala, Firouzeh Korangy, David E Kleiner, William D Figg, David Venzon, Seth M Steinberg, Aradhana M Venkatesan, Venkatesh Krishnasamy, Nadine Abi-Jaoudeh, Elliot Levy, Brad J Wood, Tim F Greten
BACKGROUND: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 on the surface of activated T lymphocytes. Ablative therapies have been shown to induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced HCC. METHODS: Patients with HCC [Childs Pugh A/B7; Barcelona Clinic Liver Cancer Stage B/C; ECOG 0/1] were enrolled in a study of tremelimumab in combination with an ablative procedure performed during week 6...
November 2, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27807226/subcellular-localizations-of-rig-i-trim25-and-mavs-complexes
#20
M T Sánchez-Aparicio, J Ayllón, A Leo-Macias, T Wolff, A García-Sastre
: The RIG-I signaling pathway is essential for the recognition of viruses and the initiation of host IFN-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds MAVS, leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway, through the use of Bimolecular Fluorescence Complementation (BiFC) and super resolution microscopy. Dimers of RIG-I, TRIM25 and MAVS localize into different compartments...
November 2, 2016: Journal of Virology
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