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Immune response to HCV

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https://www.readbyqxmd.com/read/29138492/the-antigenic-variability-of-hcv-in-viral-hla-ag-binding-is-related-to-the-activation-of-the-host-immune-response
#1
P Muñoz de Rueda, S M Jiménez-Ruiz, R Quiles, E J Pavón-Castillero, J A Muñoz-Gámez, J Casado, A Gila, A Ruiz-Extremera, J Salmerón
Our previous data show that hepatitis C virus (HCV) genotype 1 patients expressing the HLA-DQB1 * 0301 allele have a combined response probability of 69%, while the remaining 31% do not respond, probably because the HCV immunodominant epitope (IE) against the DQB1 * 0301 allele is mutated. HCV IE (region sequenced in NS3 is a region encoding aa 1253-1272) from 37 patients (21 Sustained Virological Response, SVR; 16 non-SVR) HLA-DQB1 * 0301+, were analysed by pyrosequencing. In vitro cultures were also determined by CD4+ proliferation, using non-mutated IE (wild-type synthetic peptide) and synthetic mutated peptide...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120581/serum-mannose-binding-lectin-in-egyptian-patients-with-chronic-hepatitis-c
#2
Laila M Yousef, Hesham M Hefny, Asmaa N Mohammad
Approximately 60 - 85% of HCV infections cannot eradicate the virus and progress to chronic hepatitis, this may be explained by failure in host immune responses or by the ability of HCV to defeat host defense mechanisms. Mannose-binding lectin (MBL) may play an immunomodulatory role. This work intended to evaluate the relationship of MBL concentration to chronic HCV infection. Two groups, a patient group (n=50) with chronic hepatitis C, and a control group, (n=35) apparently healthy non-infected subjects were studied...
January 2017: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/29119112/expression-and-immunogenicity-of-two-recombinant-fusion-proteins-comprising-foot-and-mouth-disease-virus-structural-protein-vp1-and-dc-sign-binding-glycoproteins
#3
Xinsheng Liu, Jianliang Lv, Yuzhen Fang, Peng Zhou, Yanzhen Lu, Li Pan, Zhongwang Zhang, Junwu Ma, Yongguang Zhang, Yonglu Wang
Improving vaccine immunogenicity by targeting antigens to dendritic cells has recently emerged as a new design strategy in vaccine development. In this study, the VP1 gene of foot-and-mouth disease virus (FMDV) serotype A was fused with the gene encoding human immunodeficiency virus (HIV) membrane glycoprotein gp120 or C2-V3 domain of hepatitis C virus (HCV) envelope glycoprotein E2, both of which are DC-SIGN-binding glycoproteins. After codon optimization, the VP1 protein and the two recombinant VP1-gp120 and VP1-E2 fusion proteins were expressed in Sf9 insect cells using the insect cell-baculovirus expression system...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29118372/human-single-chain-transbodies-that-bound-to-domain-i-of-non-structural-protein-5a-ns5a-of-hepatitis-c-virus
#4
Kittirat Glab-Ampai, Monrat Chulanetra, Aijaz Ahmad Malik, Thanate Juntadech, Jeeraphong Thanongsaksrikul, Potjanee Srimanote, Kanyarat Thueng-In, Nitat Sookrung, Pongsri Tongtawe, Wanpen Chaicumpa
A safe and broadly effective direct acting anti-hepatitis C virus (HCV) agent that can withstand the viral mutation is needed. In this study, human single chain antibody variable fragments (HuscFvs) to conserved non-structural protein-5A (NS5A) of HCV were produced by phage display technology. Recombinant NS5A was used as bait for fishing-out the protein bound-phages from the HuscFv-phage display library. NS5A-bound HuscFvs produced by five phage transfected-E. coli clones were linked molecularly to nonaarginine (R9) for making them cell penetrable (become transbodies)...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100993/hepatitis-c-virus-induced-natural-killer-cell-proliferation-involves-monocyte-derived-cells-and-the-ox40-ox40l-axis
#5
Julia Pollmann, Jana-Julia Götz, Daniel Rupp, Otto Strauss, Markus Granzin, Oliver Grünvogel, Pascal Mutz, Catharina Kramer, Felix Lasitschka, Volker Lohmann, Niklas K Björkström, Robert Thimme, Ralf Bartenschlager, Adelheid Cerwenka
BACKGROUND AND AIMS: Natural killer (NK) cells are found at increased frequencies in hepatitis C virus (HCV)-infected patients. NK cell activation was shown to correlate with HCV clearance and to predict favourable treatment response. The aim of our study was to dissect mechanisms leading to NK cell activation and proliferation in response to HCV. METHODS: NK cell phenotype, proliferation, and function were assessed after six-day co-culture of human peripheral blood mononuclear cells (PBMCs) with HCV-replicon containing Huh6 hepatoblastoma cells or HCV-infected Huh7...
October 31, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29093082/according-to-hcv-infection-stage-il-7-plus-4-1bb-triggering-alone-or-combined-with-pd-1-blockade-increases-traf1-low-hcv-specific-cd8-cell-reactivity
#6
Elia Moreno-Cubero, Dolores Subirá, Eduardo Sanz-de-Villalobos, Trinidad Parra-Cid, Antonio Madejón, Joaquín Miquel, Antonio Olveira, Alejandro González-Praetorius, Javier García-Samaniego, Juan-Ramón Larrubia
Hepatitis C virus (HCV)-specific CD8(+) T cells suffer a progressive exhaustion during persistent HCV infection (PI). This process could involve the positive immune checkpoint 4-1BB/4-1BBL, through the loss of its signal transducer TRAF1. To address this issue, peripheral HCV-specific CD8(+) T cells (Pentamer(+)/CD8(+)) from patients with PI and resolved infection after treatment (RI) were studied. Duration of HCV infection and liver fibrosis progression rate inversely correlated with the likelihood of detecting peripheral pentamer(+)/CD8(+) cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29089195/superior-immunogenicity-of-hcv-envelope-glycoproteins-when-adjuvanted-with-cyclic-di-amp-a-sting-activator-or-archaeosomes
#7
A Landi, J Law, D Hockman, M Logan, K Crawford, C Chen, J Kundu, T Ebensen, C A Guzman, L Deschatelets, L Krishnan, D L J Tyrrell, M Houghton
Three decades after the discovery, hepatitis C virus (HCV) is still the leading cause of liver transplantation and poses a major threat to global health. In spite of recent advances in the development of direct acting antivirals, there is still a need for a prophylactic vaccine to limit the virus spread and protect at-risk populations, especially in developing countries, where the cost of the new treatments may severely limit access. The use of recombinant HCV glycoproteins E1E2 (rE1E2) in combination with the MF59, an oil-in-water emulsion-based adjuvant, has previously been shown to reduce the rate of chronicity in chimpanzees and to induce production of cross-neutralizing antibodies and cellular immune responses in human volunteers...
October 28, 2017: Vaccine
https://www.readbyqxmd.com/read/29084047/infection-by-htlv-1-is-associated-with-high-levels-of-pro-inflammatory-cytokines-in-hiv-hcv-coinfected-patients
#8
Carlos Brites, Marcos Abrahão, Patrícia Bozza, Eduardo M Netto, André Lyra, Fabianna Bahia
OBJECTIVES: HIV, HCV, and HTLV-1 share the same routes of infection, making coinfection by these viruses a frequent finding in endemic areas. However, there is scarce information on the clinical / immunological consequences of triple infection. Coinfection by HTLV-1 is able to modulate cytokine´s production in HIV patients, but there is no data on the immune response of HIV-HCV-HTLV-1 infected patients METHODS:: we compared the plasma levels of 25 different cytokines in HIV-HCV patients, according to their serostatus to HTLV-1 infection...
October 27, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29064582/establishment-of-a-platform-for-molecular-and-immunological-characterization-of-the-rna-dependent-rna-polymerase-ns5b-of-an-egyptian-hcv-isolate
#9
Hossam Gewaid, Ahmed A Mesalam, Ahmed A Ibrahim, Dina N Abdel Shafy, Rola N Abdel Shafy, Nahed Emara, Soha M Hamdy, Mohy Gewaid, Mahmoud M Bahgat
The present work aimed at establishing a platform to enable frequent characterization of the HCV RNA-dependent-RNA-polymerase from Egyptian clinical isolates. Subjecting amplified HCV-NS5B coding gene from Egyptian patient's serum to sequencing, multiple alignment and phylogenetic analysis confirmed its subtype 4a origin. Nucleotide sequence analysis revealed presence of an additional start codon at the beginning of the NS5B gene. Peptide sequence alignment demonstrated presence of unique amino acid residues in our 4a-NS5B sequence distinct from the JFH-1-NS5B sequence as well as unique amino acids compared to other genotypes...
October 24, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29063663/enhanced-natural-killer-cell-activity-is-found-in-exposed-uninfected-recipients-of-hepatitis-c-contaminated-blood
#10
Maggie M Ow, Doha Hegazy, Usama M Warshow, Matthew E Cramp
A minority of injecting drug users, termed exposed uninfected, are resistant to hepatitis C (HCV) infection despite repeated low-dose exposures. We identify for the first time a cohort of blood recipients who remained uninfected despite large-dose exposure to HCV-contaminated blood and characterise immune factors that may confer protection. Of 1340 blood recipients from the English Look Back database who were transfused HCV-contaminated blood, we identified 8 who remained uninfected. In these 8 exposed uninfecteds, we characterised their natural killer (NK) cell populations and HCV-specific T cell responses...
October 24, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29052135/hepatitis-c-virus-associated-cancers
#11
Zhigang Yi, Zhenghong Yuan
Most hepatitis C virus (HCV) infection results in persistent infection. Significant portion of chronic HCV-infected patients develop hepatocellular carcinoma (HCC). Chronic hepatitis C is also associated with extrahepatic manifestations, including cryoglobulinemia, lymphoma, insulin resistance, type 2 diabetes, and neurological disorders. The molecular mechanisms of how HCV infection causes liver cancer are largely unknown. HCV replication or viral proteins may perturb cellular hemostasis and induce the generation of reactive oxygen species (ROS); viral components or viral replication products act as agonist to trigger innate immune response and cause chronic inflammation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29045731/the-chimpanzee-model-of-viral-hepatitis-advances-in-understanding-the-immune-response-and-treatment-of-viral-hepatitis
#12
Robert E Lanford, Christopher M Walker, Stanley M Lemon
Chimpanzees (Pan troglodytes) have contributed to diverse fields of biomedical research due to their close genetic relationship to humans and in many instances due to the lack of any other animal model. This review focuses on the contributions of the chimpanzee model to research on hepatitis viruses where chimpanzees represented the only animal model (hepatitis B and C) or the most appropriate animal model (hepatitis A). Research with chimpanzees led to the development of vaccines for HAV and HBV that are used worldwide to protect hundreds of millions from these diseases and, where fully implemented, have provided immunity for entire generations...
October 17, 2017: ILAR Journal
https://www.readbyqxmd.com/read/29045541/from-hepatitis-c-virus-infection-to-b-cell-lymphoma
#13
L Couronné, E Bachy, S Roulland, B Nadel, F Davi, M Armand, D Canioni, J M Michot, C Visco, L Arcaini, C Besson, O Hermine
In addition to liver disorders, Hepatitis C virus (HCV) is also associated with extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL), especially marginal zone lymphoma, de novo or transformed diffuse large B-cell lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and clinical observations argue for an association between HCV and lymphoproliferative disorders. The causative role of HCV in NHL has been further supported by the response to anti-viral therapy. Pathophysiological processes at stake leading from HCV infection to overt lymphoma still need to be further elucidated...
October 10, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29040985/serum-ifn-%C3%AE-3-levels-correlate-with-serum-hepatitis-c-virus-rna-levels-in-symptomatic-patients-with-acute-hepatitis-c
#14
Susumu Imoto, Soo Ryang Kim, Keisuke Amano, Etsuko Iio, Seitetsu Yoon, Shigeya Hirohata, Yoshihiko Yano, Toru Ishikawa, Shinji Katsushima, Toshiki Komeda, Toyokazu Fukunaga, Hobyung Chung, Hiroyuki Kokuryu, Yutaka Horie, Takashi Hatae, Aya Fujinami, Soo Ki Kim, Masatoshi Kudo, Yasuhito Tanaka
BACKGROUND: Recent genome-wide association studies demonstrated that 2 single nucleotide polymorphisms (SNPs), upstream of the interferon-λ (IFNL) 3 gene, are associated with the spontaneous clearance of hepatitis C virus (HCV) in symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs, rs8099917 and rs12979860, have established their significant roles in the innate immunity response to spontaneously clear HCV in patients with AHC, the detailed mechanisms of their roles remain largely unknown...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29033929/immunity-and-fibrogenesis-the-role-of-th17-il-17-axis-in-hbv-and-hcv-induced-chronic-hepatitis-and-progression-to-cirrhosis
#15
REVIEW
Feliciano Chanana Paquissi
Cirrhosis is a common final pathway for most chronic liver diseases; representing an increasing burden worldwide and is associated with increased morbidity and mortality. Current evidence has shown that, after an initial injury, the immune response has a significant participation in the ongoing damage, and progression from chronic viral hepatitis (CVH) to cirrhosis, driving the activation and maintenance of main fibrogenic pathways. Among immune deregulations, those related to the subtype 17 of T helper lymphocytes (Th17)/interleukin-17 (IL-17) axis have been recognized as key immunopathological and prognostic elements in patients with CVH...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033906/long-non-coding-rnas-in-hepatitis-c-virus-infected-cells
#16
REVIEW
Marina Barriocanal, Puri Fortes
Hepatitis C virus (HCV) often leads to a chronic infection in the liver that may progress to steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Several viral and cellular factors are required for a productive infection and for the development of liver disease. Some of these are long non-coding RNAs (lncRNAs) deregulated in infected cells. After HCV infection, the sequence and the structure of the viral RNA genome are sensed to activate interferon (IFN) synthesis and signaling pathways. These antiviral pathways regulate transcription of several cellular lncRNAs...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29029951/intrahepatic-v%C3%AE-9v%C3%AE-2-t-cells-from-hcv-infected-patients-show-an-exhausted-phenotype-but-can-inhibit-hcv-replication
#17
E Cimini, V Bordoni, A Sacchi, U Visco-Comandini, M Montalbano, C Taibi, R Casetti, E Lalle, G D'Offizi, M R Capobianchi, C Agrati
Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction. Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCV(pos)) and in HCV-negative (HCV(neg)) subjects. Phenotypic and functional analysis was performed by flow cytometry...
October 10, 2017: Virus Research
https://www.readbyqxmd.com/read/29027943/low-grade-dysplastic-nodules-revealed-as-the-tipping-point-during-multistep-hepatocarcinogenesis-by-dynamic-network-biomarkers
#18
Lina Lu, Zhonglin Jiang, Yulin Dai, Luonan Chen
Hepatocellular carcinoma (HCC) is a complex disease with a multi-step carcinogenic process from preneoplastic lesions, including cirrhosis, low-grade dysplastic nodules (LGDNs), and high-grade dysplastic nodules (HGDNs) to HCC. There is only an elemental understanding of its molecular pathogenesis, for which a key problem is to identify when and how the critical transition happens during the HCC initiation period at a molecular level. In this work, for the first time, we revealed that LGDNs is the tipping point (i...
October 13, 2017: Genes
https://www.readbyqxmd.com/read/28991189/translational-implication-of-galectin-9-in-the-pathogenesis-and-treatment-of-viral-infection
#19
REVIEW
Jenn-Haung Lai, Shue-Fen Luo, Mei-Yi Wang, Ling-Jun Ho
The interaction between galectin-9 and its receptor, Tim-3, triggers a series of signaling events that regulate immune responses. The expression of galectin-9 has been shown to be increased in a variety of target cells of many different viruses, such as hepatitis C virus (HCV), hepatitis B virus (HBV), herpes simplex virus (HSV), influenza virus, dengue virus (DENV), and human immunodeficiency virus (HIV). This enhanced expression of galectin-9 following viral infection promotes significant changes in the behaviors of the virus-infected cells, and the resulting events tightly correlate with the immunopathogenesis of the viral disease...
October 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28978808/monoclonal-igg-in-mgus-and-multiple-myeloma-targets-infectious-pathogens
#20
Adrien Bosseboeuf, Delphine Feron, Anne Tallet, Cédric Rossi, Cathy Charlier, Laurent Garderet, Denis Caillot, Philippe Moreau, Marina Cardó-Vila, Renata Pasqualini, Wadih Arap, Alfreda Destea Nelson, Bridget S Wilson, Hélène Perreault, Eric Piver, Pierre Weigel, François Girodon, Jean Harb, Edith Bigot-Corbel, Sylvie Hermouet
Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens...
October 5, 2017: JCI Insight
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