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Immune response to HCV

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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
#1
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/28434648/nivolumab-in-patients-with-advanced-hepatocellular-carcinoma-checkmate-040-an-open-label-non-comparative-phase-1-2-dose-escalation-and-expansion-trial
#2
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/28419665/lettuce-produced-hepatitis-c-virus-e1e2-heterodimer-triggers-immune-responses-in-mice-and-antibody-production-after-oral-vaccination
#3
Jihong Liu Clarke, Lisa Paruch, Mihaela-Olivia Dobrica, Iuliana Caras, Catalin Tucureanu, Adrian Onu, Sonya Ciulean, Crina Stavaru, Andre Eerde, Yanliang Wang, Hege Steen, Sissel Haugslien, Catalina Petrareanu, Catalin Lazar, Ioan Popescu, Ralph Bock, Jean Dubuisson, Norica Branza-Nichita
The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g., cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500,000 die yearly from HCV-related liver pathologies. To date, there is no licenced vaccine available to prevent HCV infection and production of an HCV vaccine remains a major challenge. Here we report the successful production of the HCV E1E2 heterodimer, an important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using Agrobacterium-mediated transient expression technology...
April 17, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28419653/hcv-viremia-associates-with-nk-cell-activation-and-dysfunction-in-anti-retroviral-hiv-hcv-co-infected-subjects
#4
E Papasavvas, L Azzoni, X Yin, Q Liu, J Joseph, A Mackiewicz, B Ross, K M Lynn, J M Jacobson, K Mounzer, J R Kostman, L J Montaner
The impact of Hepatitis C virus (HCV) RNA levels on immune status in chronically HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy (ART) remains poorly understood. A total of 78 African American subjects HCV viremic/naïve to HCV treatment (33 HCV genotype 1 mono-infected, 45 HCV genotype 1/HIV co-infected on ART) were studied. Clinical and liver enzymes measurements were performed. Whole blood was analyzed for immune subset changes by flow-cytometry. Peripheral blood mononuclear cells (PBMC) were used for same-day constitutive and in vitro Interferon (IFN)-α-induced Signal Transducer and Activator of Transcription (STAT) phosphorylation, K562 target cell lysis and K562 target cell recognition-mediated IFN-γ production...
April 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28417047/clinical-significance-of-snp-rs2596542-in-histocompatibility-complex-class-i-related-gene-a-promoter-region-among-hepatitis-c-virus-related-hepatocellular-carcinoma-cases
#5
Amal A Mohamed, Ola M Elsaid, Eman A Amer, Heba H Elosaily, Mohamed I Sleem, Shawkat S Gerges, Mohamed A Saleh, Amal El Shimy, Yasmine S El Abd
The major histocompatibility complex class I-related gene A (MICA) is an antigen induced by stress and performs an integral role in immune responses as an anti-infectious and antitumor agent. This work was designed to investigate whether (SNP) rs2596542C/T in MICA promoter region is predictive of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) or not. Forty-seven healthy controls and 94 HCV-infected patients, subdivided into 47 LC and 47 HCC subjects were enrolled in this study. SNP association was studied using real time PCR and soluble serum MICA concentration was measured using ELISA...
July 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28414566/the-changed-proportion-of-cd45ra-cd45ro-t-cells-in-chronic-hepatitis-c-patients-during-pegylated-interferon-%C3%AE-with-ribavirin-therapy
#6
Jung-Lung Hsiao, Wang-Sheng Ko, Chia-Ju Shih, Ya-Ling Chiou
Infection with the hepatitis C virus (HCV) may progress toward chronic hepatitis, liver cirrhosis, and liver cancer. A therapy for patients with chronic HCV infection is the combination of pegylated interferon-α with ribavirin, which increases the rate of sustained virological response (SVR) to 56%. However, a practical biomarker to predict SVR is lacking. T cells expressing the CD45RA isoform are considered naive, and antigenic stimulation converts them to CD45RO(+). CD45RO(+) T cells exhibit immediate response and high lymphokine production, leading to the maintenance and upregulation of immune reactions...
April 17, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28410411/hepatitis-c-virus-impairs-natural-killer-cell-activity-via-viral-serine-protease-ns3
#7
Chang Mo Yang, Joo Chun Yoon, Jeon Han Park, Jae Myun Lee
Hepatitis C virus (HCV) infection is characterized by a high frequency of chronic cases owing to the impairment of innate and adaptive immune responses. The modulation of natural killer (NK) cell functions by HCV leads to an impaired innate immune response. However, the underling mechanisms and roles of HCV proteins in this immune evasion are controversial, especially in the early phase of HCV infection. To investigate the role of HCV nonstructural proteins especially NS3 in the impairment of NK functions, NK cells were isolated from the PBMCs by negative selection...
2017: PloS One
https://www.readbyqxmd.com/read/28402927/hepatitis-c-virus-inflammation-and-cellular-aging-turning-back-time
#8
REVIEW
Susanna Naggie
There is evidence that hepatitis C virus (HCV) infection, like HIV infection, may be associated with chronic inflammation, immune activation, and immune senescence, which contribute to increased risks for cardiometabolic or other diseases outside the liver, as well as to ongoing damage in the liver. These effects may persist after a sustained virologic response (SVR) is achieved with HCV therapy. Such findings support initiation of treatment for HCV-infected individuals before damage to the liver is apparent and monitoring of individuals for complications even after an SVR is achieved...
February 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28402196/mice-antibody-response-to-conserved-nonadjuvanted-multiple-antigenic-peptides-derived-from-e1-e2-regions-of-hepatitis-c-virus
#9
Tawfeek H Abdelhafez, Noha G Bader El Din, Ashraf A Tabll, Mohammad M Mashaly, Reham M Dawood, Nemat A Yassin, Mostafa K El-Awady
Synthetic peptides are one of the hepatitis C virus (HCV)-specific small molecules that have antiviral activity and represent a target for HCV vaccine. This study aims to determine the lowest concentration of adjuvanted and non-adjuvanted (multiple antigenic peptide [MAP]) form of three conserved HCV envelope peptides that can induce murine immunogenic responses and evaluate the neutralization capacities of the generated antibodies (Abs) against HCV in cultured Huh7.5 cells. In this study, three HCV synthetic peptides, E1 peptide (a...
April 12, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28398489/immunization-with-a-subunit-hepatitis-c-virus-vaccine-elicits-pan-genotypic-neutralizing-antibodies-and-intra-hepatic-t-cell-responses-in-non-human-primates
#10
Dapeng Li, Xuesong Wang, Markus von Schaewen, Wanyin Tao, Yunfang Zhang, Brigitte Heller, Gabriela Hrebikova, Qiang Deng, Qiang Sun, Alexander Ploss, Jin Zhong, Zhong Huang
Background: The global control of hepatitis C virus (HCV) infection remains a great burden, due to the high prices and potential drug resistance of the new direct-acting antivirals (DAAs) as well as the risk of reinfection in DAA-cured patients. Thus, a prophylactic vaccine for HCV is of great importance. We previously reported a single recombinant soluble E2 (sE2) vaccine produced in insect cells was able to induce broadly neutralizing antibodies (NAbs) and prevent HCV infection in mice...
April 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28394926/gp73-represses-host-innate-immune-response-to-promote-virus-replication-by-facilitating-mavs-and-traf6-degradation
#11
Xuewu Zhang, Chengliang Zhu, Tianci Wang, Hui Jiang, Yahui Ren, Qi Zhang, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients' serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28391873/il-10-and-il-28b-gene-variants-as-predictors-of-sustained-response-to-peginterferon-and-ribavirin-therapy-in-chronic-hcv-infection
#12
Ikram Sghaier, Leila Mouelhi, Noor A Rabia, Ezzedine Ghazoueni, Wassim Y Almawi, Besma Yacoubi Loueslati
OBJECTIVES: Interleukin-10 (IL-10) plays an important role in the immunity to hepatitis C virus (HCV). Insofar as IL-10 variants are associated with altered levels of IL-10, previous studies that examined the association of IL-10 polymorphisms with the susceptibility to and progression of chronic HCV, and response to anti-viral treatment were inconsistent. We investigated the association between common IL-10 variants in the intron and the promotor region with HCV and associated features...
April 5, 2017: Cytokine
https://www.readbyqxmd.com/read/28389568/hepatitis-c-virus-triggers-golgi-fragmentation-and-autophagy-through-the-immunity-related-gtpase-m
#13
Marianne D Hansen, Ingvild B Johnsen, Kim A Stiberg, Tatyana Sherstova, Takaji Wakita, Gabriel Mary Richard, Richard K Kandasamy, Eliane F Meurs, Marit W Anthonsen
Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase M (IRGM), known to contribute to autophagy, plays a previously unrecognized role in this process. We show that IRGM is localized at the Golgi apparatus and regulates the fragmentation of Golgi membranes in response to HCV infection, leading to colocalization of Golgi vesicles with replicating HCV...
April 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28388935/direct-acting-antiviral-agents-in-the-therapy-of-hepatitis-c-virus-related-mixed-cryoglobulinaemia-a-single-centre-experience
#14
Gianfranco Lauletta, Sabino Russi, Fabio Pavone, Angelo Vacca, Franco Dammacco
BACKGROUND: The efficacy and safety of direct-acting antiviral agents (DAAs) were evaluated in a cohort of prospectively enrolled patients with hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC), an immune complex-mediated vasculitis of small and medium vessels in which the pathogenetic role of HCV has been clearly established. METHODS: Twenty-two patients received DAAs. Clinical and laboratory features were recorded at baseline, every 4 weeks until the end of treatment (EoT), and 12 weeks afterwards...
April 8, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28384290/mait-cells-are-reduced-in-frequency-and-functionally-impaired-in-human-t-lymphotropic-virus-type-1-infection-potential-clinical-implications
#15
Dominic Paquin-Proulx, Benjamin C Greenspun, Emanuela A S Costa, Aluisio C Segurado, Esper G Kallas, Douglas F Nixon, Fabio E Leal
HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection...
2017: PloS One
https://www.readbyqxmd.com/read/28360091/transcriptional-response-to-hepatitis-c-virus-infection-and-interferon-alpha-treatment-in-the-human-liver
#16
Tujana Boldanova, Aleksei Suslov, Markus H Heim, Anamaria Necsulea
Hepatitis C virus (HCV) is widely used to investigate host-virus interactions. Cellular responses to HCV infection have been extensively studied in vitro However, in human liver, interferon (IFN)-stimulated gene expression can mask direct transcriptional responses to infection. To better characterize the direct effects of HCV infection in vivo, we analyze the transcriptomes of HCV-infected patients lacking an activated endogenous IFN system. We show that expression changes observed in these patients predominantly reflect immune cell infiltrates rather than cell-intrinsic pathways...
March 30, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28339063/viral-and-host-factors-associated-with-outcomes-of-hepatitis-c-virus-infection-review
#17
Zehui Yan, Yuming Wang
Hepatitis C virus (HCV) infection is a major health issue globally. Owing to the progress made in host genetics and HCV molecular virology, emerging data have suggested that the natural course and treatment response in patients with HCV infection are largely determined by complex host‑viral interactions. HCV genotype is the most important viral factor predicting the response to pegylated interferon‑α plus ribavirin therapy. The subtype of HCV genotype 1 is the key viral factor that predicts the efficacy of direct‑acting antiviral therapy...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28332476/new-onset-hepatitis-c-virus-associated-glomerulonephritis-following-sustained-virologic-response-with-direct-acting-antiviral-therapy%C3%A2
#18
Muriel Ghosn, Matthew B Palmer, Catherine E Najem, Danny Haddad, Peter A Merkel, Jonathan J Hogan
Glomerulonephritis (GN) is an important extra-hepatic manifestation of infection with hepatitis C virus (HCV). HCV-associated GN occurs due to HCV-induced lymphoproliferation, leading to the generation of pathogenic immune complexes, including complexes containing cryoglobulins. The management of HCV-associated extra-hepatic disease is focused on viral eradication, with direct-acting antiviral agents leading to high rates of sustained virologic remission. There have been a few reports of relapsing cryoglobulinemic vasculitis after sustained virologic remission was achieved with interferon-based therapies...
March 23, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28300059/genetic-basis-for-variation-in-plasma-il-18-levels-in-persons-with-chronic-hepatitis-c-virus-and-human-immunodeficiency-virus-1-infections
#19
C Vergara, C Thio, R Latanich, A L Cox, G D Kirk, S H Mehta, M Busch, E L Murphy, M C Villacres, M G Peters, A L French, E Golub, J Eron, C D Lahiri, S Shrestha, D Gustafson, M Young, K Anastos, B Aouizerat, A Y Kim, G Lauer, D L Thomas, P Duggal
Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade...
March 16, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28295920/importin-%C3%AE-1-targeting-by-hepatitis-c-virus-ns3-4a-protein-restricts-irf3-and-nf-%C3%AE%C2%BAb-signaling-of-ifnb1-antiviral-response
#20
Bridget Gagné, Nicolas Tremblay, Alex Y Park, Martin Baril, Daniel Lamarre
In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-β (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection...
March 13, 2017: Traffic
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