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Immune response to HCV

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https://www.readbyqxmd.com/read/29782532/hepatitis-c-virus-ns4b-induces-the-degradation-of-trif-to-inhibit-tlr3-mediated-interferon-signaling-pathway
#1
Yisha Liang, Xuezhi Cao, Qiang Ding, Yanan Zhao, Zhenliang He, Jin Zhong
Toll-like receptor 3 (TLR3) senses dsRNA intermediates produced during RNA virus replication to activate innate immune signaling pathways through adaptor protein TRIF. Many viruses have evolved strategies to block TLR3-mediated interferon signaling via targeting TRIF. Here we studied how hepatitis C virus (HCV) antagonizes the TLR3-mediated interferon signaling. We found that HCV-encoded NS4B protein inhibited TLR3-mediated interferon signaling by down-regulating TRIF protein level. Mechanism studies indicated that the downregulation of TRIF by NS4B was dependent on caspase8...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29755477/glycan-shielding-and-modulation-of-hepatitis-c-virus-neutralizing-antibodies
#2
REVIEW
Muriel Lavie, Xavier Hanoulle, Jean Dubuisson
Hepatitis C virus (HCV) envelope glycoprotein heterodimer, E1E2, plays an essential role in virus entry and assembly. Furthermore, due to their exposure at the surface of the virion, these proteins are the major targets of anti-HCV neutralizing antibodies. Their ectodomain are heavily glycosylated with up to 5 sites on E1 and up to 11 sites on E2 modified by N-linked glycans. Thus, one-third of the molecular mass of E1E2 heterodimer corresponds to glycans. Despite the high sequence variability of E1 and E2, N-glycosylation sites of these proteins are generally conserved among the seven major HCV genotypes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29744934/modelling-how-reversal-of-immune-exhaustion-elicits-cure-of-chronic-hepatitis-c-after-the-end-of-treatment-with-direct-acting-antiviral-agents
#3
Subhasish Baral, Rahul Roy, Narendra M Dixit
A fraction of chronic hepatitis C patients treated with direct-acting antivirals (DAAs) achieved sustained virological responses (SVR), or cure, despite having detectable viremia at the end of treatment (EOT). This observation, termed EOT+ /SVR, remains puzzling and precludes rational optimization of treatment durations. One hypothesis to explain EOT+ /SVR, the immunologic hypothesis, argues that the viral decline induced by DAAs during treatment reverses the exhaustion of cytotoxic T lymphocytes (CTLs), which then clear the infection after treatment...
May 9, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29740042/evidence-of-cd4-t-cell-mediated-immune-pressure-on-the-hepatitis-c-virus-genome
#4
Michaela Lucas, Pooja Deshpande, Ian James, Andri Rauch, Katja Pfafferott, Elouise Gaylard, Shahzma Merani, Anne Plauzolles, Andrew Lucas, Wyatt McDonnell, Spyros Kalams, Mark Pilkinton, Cody Chastain, Louise Barnett, Amy Prosser, Simon Mallal, Karen Fitzmaurice, Heidi Drummer, M Azim Ansari, Vincent Pedergnana, Ellie Barnes, Mina John, Dermot Kelleher, Paul Klenerman, Silvana Gaudieri
Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4+ T cells...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29734473/treatment-for-hepatitis-c-virus-associated-mixed-cryoglobulinaemia
#5
REVIEW
Nuria Montero, Alexandre Favà, Eva Rodriguez, Clara Barrios, Josep M Cruzado, Julio Pascual, Maria Jose Soler
BACKGROUND: Hepatitis C virus (HCV)-associated mixed cryoglobulinaemia is the manifestation of an inflammation of small and medium-sized vessels produced by a pathogenic IgM with rheumatoid factor activity generated by an expansion of B-cells. The immune complexes formed precipitate mainly in the skin, joints, kidneys or peripheral nerve fibres. Current therapeutic approaches are aimed at elimination of HCV infection, removal of cryoglobulins and also of the B-cell clonal expansions. The optimal treatment for it has not been established...
May 7, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29706960/macrophage-derived-extracellular-vesicles-induce-long-lasting-immunity-against-hepatitis-c-virus-which-is-blunted-by-polyunsaturated-fatty-acids
#6
Chengcong Cai, Benjamin Koch, Kenichi Morikawa, Goki Suda, Naoya Sakamoto, Sabrina Rueschenbaum, Sami Akhras, Julia Dietz, Eberhard Hildt, Stefan Zeuzem, Christoph Welsch, Christian M Lange
Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. In this study, we aimed to further characterize the role of macrophage-derived EVs in immune responses against hepatitis C virus (HCV) and the potential of polyunsaturated fatty acids (PUFAs) to modulate this modality of innate immunity. To this end, EVs were isolated from interferon-stimulated macrophage cultures or from serum of patients with acute or chronic hepatitis C. EVs were characterized by electron microscopy, flow cytometry, RNA-sequencing, and Western blot analysis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29705529/long-term-outcomes-of-patients-with-hcv-associated-cryoglobulinemic-vasculitis-after-virologic-cure
#7
Martín Bonacci, Sabela Lens, Zoe Mariño, María-Carlota Londoño, Sergio Rodriguez-Tajes, José M Sánchez-Tapias, Manel Ramos-Casals, José Hernández-Rodríguez, Xavier Forns
Patients with hepatitis C virus-associated cryoglobulinemic vasculitis (HCV-CV) have high rates of clinical remission after treatment with direct-acting antivirals (DAAs),but circulating cryoglobulins persist and vascular disorders reappear in some patients shortly after DAA treatment ends. We performed a prospective study to assess the long-term clinical and immune system effects of HCV eradication with DAAs in 46 patients with HCV-CV and 42 asymptomatic patients with circulating cryoglobulins. A median of 24 months after DAA treatment (range, 17-41 months), 66% of patients with HCV-CV and 70% of asymptomatic patients with circulating cryoglobulins had immunologic response, with comparable reductions in cryocrit from 2...
April 26, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29705238/hcv-modifies-egf-signalling-and-upregulates-production-of-cxcr2-ligands-role-in-inflammation-and-antiviral-immune-response
#8
Christina Groepper, Kerstin Rufinatscha, Nadja Schröder, Sabine Stindt, Christian Ehlting, Ute Albrecht, Hans H Bock, Ralf Bartenschlager, Dieter Häussinger, Johannes G Bode
BACKGROUND & AIMS: To affect immune response and inflammation, the hepatitis C virus (HCV) substantially influences intercellular communication pathways that are decisive for immune cell recruitment. The present study investigates mechanisms by which HCV modulates chemokine-mediated intercellular communication of the infected cells. METHODS: Chemokine expression is studied in HCVcc -infected cell lines or cell lines harbouring a subgenomic replicon as well as in serum samples from patients...
April 26, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29704252/baseline-intrahepatic-and-peripheral-innate-immunity-are-associated-with-hepatitis-c-virus-clearance-during-daa-therapy
#9
Hawwa Alao, Maggie Cam, Chithra Keembiyehetty, Fang Zhang, Elisavet Serti, Daniel Suarez, Heiyoung Park, Nicolaas H Fourie, Elizabeth C Wright, Wendy A Henderson, Qisheng Li, T Jake Liang, Barbara Rehermann, Marc G Ghany
OBJECTIVE: Hepatitis C virus (HCV) infection induces interferon-stimulated genes (ISGs) and downstream innate immune responses. This study investigated whether baseline and on-treatment differences in these responses predict response versus virological breakthrough during therapy with direct-acting antivirals (DAA). METHODS: Thirteen HCV genotype 1b-infected patients who had previously failed a course of peginterferon/ribavirin were re-treated with asunaprevir/daclatasvir for 24 weeks...
April 27, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29703495/can-broadly-neutralizing-monoclonal-antibodies-lead-to-a-hepatitis-c-virus-vaccine
#10
REVIEW
Valerie J Kinchen, Andrea L Cox, Justin R Bailey
While licensed vaccines elicit protective antibody responses against a variety of viral infections, an effective vaccine for hepatitis C virus (HCV) has remained elusive. The extraordinary genetic diversity of HCV and the ability of the virus to evade the immune response have hindered vaccine development efforts. However, recent studies have greatly expanded the number of well characterized broadly neutralizing human monoclonal antibodies (bNAbs) against HCV. These bNAbs target relatively conserved HCV epitopes, prevent HCV infection in animal models, and are associated with spontaneous clearance of human HCV infection...
April 24, 2018: Trends in Microbiology
https://www.readbyqxmd.com/read/29691437/immunological-responses-following-administration-of-a-genotype-1a-1b-2-3a-quadrivalent-hcv-vlp-vaccine
#11
D Christiansen, L Earnest-Silveira, B Chua, P Meuleman, I Boo, B Grubor-Bauk, D C Jackson, Z Y Keck, S K H Foung, H E Drummer, E J Gowans, J Torresi
The significant public health problem of Hepatitis C virus (HCV) has been partially addressed with the advent of directly acting antiviral agents (DAAs). However, the development of an effective preventative vaccine would have a significant impact on HCV incidence and would represent a major advance towards controlling and possibly eradicating HCV globally. We previously reported a genotype 1a HCV viral-like particle (VLP) vaccine that produced neutralizing antibodies (NAb) and T cell responses to HCV. To advance this approach, we produced a quadrivalent genotype 1a/1b/2a/3a HCV VLP vaccine to produce broader immune responses...
April 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29686409/vibrio-vulnificus-quorum-sensing-molecule-cyclo-phe-pro-inhibits-rig-i-mediated-antiviral-innate-immunity
#12
Wooseong Lee, Seung-Hoon Lee, Minwoo Kim, Jae-Su Moon, Geon-Woo Kim, Hae-Gwang Jung, In Hwang Kim, Ji Eun Oh, Hi Eun Jung, Heung Kyu Lee, Keun Bon Ku, Dae-Gyun Ahn, Seong-Jun Kim, Kun-Soo Kim, Jong-Won Oh
The recognition of pathogen-derived ligands by pattern recognition receptors activates the innate immune response, but the potential interaction of quorum-sensing (QS) signaling molecules with host anti-viral defenses remains largely unknown. Here we show that the Vibrio vulnificus QS molecule cyclo(Phe-Pro) (cFP) inhibits interferon (IFN)-β production by interfering with retinoic-acid-inducible gene-I (RIG-I) activation. Binding of cFP to the RIG-I 2CARD domain induces a conformational change in RIG-I, preventing the TRIM25-mediated ubiquitination to abrogate IFN production...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29684853/naringenin-improve-hepatitis-c-virus-infection-induced-insulin-resistance-by-increase-pten-expression-via-p53-dependent-manner
#13
Benli Jia, Dongsheng Yu, Gang Yu, Yunsheng Cheng, Yang Wang, Xiaoqiang Yi, Xiaoping Li, Yong Wang
Hepatitis C virus (HCV) infection may finally lead to hepatocellular carcinoma (HCC), and also associated with insulin resistance (IR). Naringenin (NGEN), a flavonoid found in grapefruit, has anti-virus, anti-inflammation and insulin sensitization effects. In the present study we examined the effects of NGEN on HCV core protein (HCVCP) infection induced IR and investigated the mechanism involved. We found that NGEN ameliorated IR and glucose tolerance in HCVCP infected mice by increase the phosphorylation of Akt at both Ser473 and Thr308 site, and also inhibited the inflammation cytokine production and T-cell immune response...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29672926/insights-into-the-etiology-associated-gene-regulatory-networks-in-hepatocellular-carcinoma-from-the-cancer-genome-atlas
#14
Veerabrahma Pratap Seshachalam, Karthik Sekar, Kam M Hui
BACKGROUND AND AIM: Hepatitis B virus, hepatitis C virus, alcoholic consumption and non-alcoholic fatty liver are the major known risk factors for Hepatocellular carcinoma (HCC). There have been very few studies comparing the underlying biological mechanisms associated with the different etiologies of HCC. In this study, we hypothesized the existence of different regulatory networks associated with different liver disease etiologies involved in hepatocarcinogenesis. METHODS: Using upstream regulatory analysis tool in ingenuity pathway analysis software, URs were predicted using differential expressed genes for HCC to facilitate the interrogation of global gene regulation...
April 19, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29665000/increased-killer-b-cells-in-chronic-hcv-infection-may-lead-to-autoimmunity-and-increased-viral-load
#15
Nasren Eiza, Eli Zuckerman, Matthias Carlebach, Tova Rainis, Yair Goldberg, Zahava Vadasz
BACKGROUND: B regulatory (Breg) cells are characterized by various membrane markers, and the secretion of different inhibitory cytokines. A new subset of Breg cells was identified as CD5hi Fas-ligand (FasL)hi. Their main reported role is to suppress anti-viral and anti-tumor immune responses and hence, they have been dubbed "killer" B cells. In this study, we aim to assess the role of these cells in chronic hepatitis C virus (HCV) infection, and determine if they contribute to the increased viral load and persistence of HCV and its related autoimmunity...
April 17, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29607354/consequence-of-hiv-and-hcv-co-infection-on-host-immune-response-persistence-and-current-treatment-options
#16
REVIEW
Sayed Sartaj Sohrab, Mohd Suhail, Ashraf Ali, Ishtiaq Qadri, Steve Harakeh, Esam I Azhar
Hepatitis C virus (HCV) is a common opportunistic pathogen especially among Human immunodeficiency virus (HIV) infected patients. Due to incongruous studies, the pathological effect of HCV on HIV induced disease are still not fully understood. While some studies have showed no effect of HCV on HIV infection, others reported a defined role of HCV in aggravating the rates of AIDS-related illnesses and mortality. The explanation of such variances may be due to the host immune response, viral genotypes, sub-type and quasi-species distribution...
March 2018: Virusdisease
https://www.readbyqxmd.com/read/29577052/frequency-of-interferon-resistance-conferring-substitutions-in-amino-acid-positions-70-and-91-of-core-protein-of-the-russian-hcv-1b-isolates-analyzed-in-the-t-cell-epitopic-context
#17
V S Kichatova, K K Kyuregyan, N V Soboleva, A A Karlsen, O V Isaeva, M G Isaguliants, M I Mikhailov
Amino acid substitutions R70Q/H and L91M in HCV subtype 1b core protein can affect the response to interferon and are associated with the development of hepatocellular carcinoma. We found that the rate of R70Q/H in HCV 1b from Russia was 31.2%, similar to that in HCV strains from Asia (34.0%), higher than that in the European (18.0%, p = 0.0010), but lower than that in the US HCV 1b strains (62.8%, p < 0.0001). Substitution L91M was found in 80.4% of the Russian HCV 1b isolates, higher than in Asian isolates (43...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29576303/neutralization-effects-of-antibody-elicited-by-chimeric-hbv-s-antigen-viral-like-particles-presenting-hcv-neutralization-epitopes
#18
Sanhua Wei, Yingfeng Lei, Jie Yang, Xiaoyan Wang, Fang Shu, Xin Wei, Fang Lin, Bin Li, Ying Cui, Hai Zhang, Sanhua Wei
Hepatitis C virus (HCV) infection is a major public health problem despite effectual direct-acting antivirals (DAAs) therapy. Development of a prophylactic vaccine is essential to block spread of HCV infection. The HBV small surface antigen (HBsAg-S) can self-assemble into virus-like particles (VLPs), has higher immunogenicity and is used as a vaccine against HBV infections. Chimeric HBsAg-S proteins with foreign epitopes allow VLP formation and induce the specific humoral and cellular immune responses against the foreign proteins...
March 22, 2018: Vaccine
https://www.readbyqxmd.com/read/29575671/rituximab-may-cause-increased-hepatitis-c-virus-viremia-in-rheumatoid-arthritis-patients-through-declining-exosomal-microrna-155
#19
Tsai-Ling Liao, Shie-Liang Hsieh, Yi-Ming Chen, Hsin-Hua Chen, Hung-Jen Liu, Hsiu-Chin Lee, Der-Yuan Chen
OBJECTIVE: Several studies observed that rituximab (RTX) may enhance hepatitis C virus (HCV) viral activity. MicroRNAs (miRNAs) have been implicated in modulating host immune response in HCV infection and then shuttled by the exosomes to exert biological functions. But the role of exosomal miRNAs in RTX-related HCV activity enhancement remains unclear. METHODS: The association between RTX and increased HCV activity was examined using an in vitro cell-based assay...
March 25, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29545925/interferon-free-treatment-for-patients-with-chronic-hepatitis-c-and-autoimmune-liver-disease-higher-svr-rates-with-special-precautions-for-deterioration-of-autoimmune-hepatitis
#20
Tatsuo Kanda, Shin Yasui, Masato Nakamura, Shingo Nakamoto, Koji Takahashi, Shuang Wu, Reina Sasaki, Yuki Haga, Sadahisa Ogasawara, Tomoko Saito, Kazufumi Kobayashi, Soichiro Kiyono, Yoshihiko Ooka, Eiichiro Suzuki, Tetsuhiro Chiba, Hitoshi Maruyama, Fumio Imazeki, Mitsuhiko Moriyama, Naoya Kato
Background: Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases. Results: All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR...
February 20, 2018: Oncotarget
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