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Immune response to HCV

Eloi R Verrier, Che C Colpitts, Charlotte Bach, Laura Heydmann, Laetitia Zona, Fei Xiao, Christine Thumann, Emilie Crouchet, Raphaël Gaudin, Camille Sureau, François-Loïc Cosset, Jane A McKeating, Patrick Pessaux, Yujin Hoshida, Catherine Schuster, Mirjam B Zeisel, Thomas F Baumert
Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3...
October 25, 2016: Cell Reports
Yanzhao Chen, Baihai Jiao, Min Yao, Xuezhen Shi, Zhebin Zheng, Shilin Li, Limin Chen
Interferon stimulated (sensitive) genes (ISGs) are the effector molecules downstream of type I/III interferon (IFN) signaling pathways in host innate immunity. ISG12a can be induced by IFN-α. Although ISG12a has been reported to inhibit the replication of HCV, the exact mechanism remains to be determined. In this study, we investigated the possible mechanisms of ISG12a anti- HCV property by exploring the production of type I IFN and the activation of Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway, apoptosis and autophagy in Huh7...
October 21, 2016: Virus Research
Anna Hojka-Osinska, Lucyna Budzko, Agnieszka Zmienko, Agnieszka Rybarczyk, Patrick Maillard, Agata Budkowska, Marek Figlerowicz, Paulina Jackowiak
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism...
October 25, 2016: Acta Biochimica Polonica
Jun P Ren, Lin Wang, Juan Zhao, Ling Wang, Shun B Ning, Mohamed El Gazzar, Jonathan P Moorman, Zhi Q Yao
Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Tregs is regulated by a miRNA-mediated mechanism...
October 18, 2016: Immunology
Mona Afify, Amal H Hamza, Reem A Alomari
To provide fundamental insights into the mechanism of Hepatitis C virus (HCV), we conduct the present study to improve further understanding of the interaction between HCV and cytokines. Two hundred one patients were enrolled in this study. Seventy-eight patients matching the study group in terms of age and gender with negative serology for hepatitis viruses, HIV virus, and with liver enzyme levels within normal range were selected as the control group. Patients were diagnosed with positive hepatitis C by detection of positive HCV antibodies in serum...
October 11, 2016: Journal of Interferon & Cytokine Research
Martín Bonacci, Sabela Lens, María-Carlota Londoño, Zoe Mariño, Maria C Cid, Manuel Ramos-Casals, Jose María Sánchez-Tapias, Xavier Forns, José Hernández-Rodríguez
BACKGROUND & AIMS: Cryoglobulins (circulating immune complexes of polyclonal IgG, monoclonal IgM, and rheumatoid factor) are detected in the circulation of 40%-60% of patients with chronic hepatitis C virus infection and cryoglobulinemic vasculitis (CV) is observed in approximately 10% of patients. We aimed to assess the clinical and immune effects of direct-acting antiviral (DAA) treatment. METHODS: We performed a prospective study of 64 patients with HCV infection with circulating cryoglobulins receiving direct-acting anti-viral therapy at a single center in Barcelona, Spain from January 2014 through April 2016...
October 7, 2016: Clinical Gastroenterology and Hepatology
Reina Sasaki, Tatsuo Kanda, Masayuki Ohtsuka, Shin Yasui, Yuki Haga, Masato Nakamura, Masayuki Yokoyama, Shuang Wu, Shingo Nakamoto, Makoto Arai, Hitoshi Maruyama, Masaru Miyazaki, Osamu Yokosuka
Direct-acting antivirals (DAAs) are relatively safe and highly effective for the eradication of hepatitis C virus (HCV) in liver transplant recipients. In this case study, we present a female with a graft reinfected with HCV genotype 2 who was treated with a combination of sofosbuvir and ribavirin after living donor liver transplantation (LDLT). Because the graft was from a hepatitis B core antibody-positive donor, passive immunization with hyperimmune hepatitis B immunoglobulin (HBIG) and entecavir were also provided to prevent hepatitis B virus (HBV) reactivation...
May 2016: Case Reports in Gastroenterology
Yaohui Wang, Yinan Jiang, Jinxue Zhou, Wuhui Song, Jing Li, Mingli Wang, Jiuge Chen, Rui Xu, Jingjing Zhang, Fanni Ma, Youhai H Chen, Yuanfang Ma
Infection of hepatitis C virus (HCV) is associated with primary hepatocellular carcinoma (HCC). However, its underlying molecular mechanisms remain enigmatic. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a new negative regulator of immunity, plays significant roles in modulating inflammation and tumorigenesis. We hypothesized that TIPE2 might be involved in the development of HCV-induced HCC. To test this hypothesis, the expression of TIPE2 was determined by Western blot in the tumor and pericarcinomatous tissues collected from ten HCV-positive HCC patients; the interaction between TIPE2 and HCV-encoded non-structural proteins was analyzed by immunoprecipitation and immunofluorescence assays, and tumorigenesis and its mechanisms were studied in cell models and nude mice...
September 30, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Stephanie T Chan, Jiyoung Lee, Mansi Narula, J-H James Ou
: Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an important adapter molecule that mediates the TNFR family and interleukin-1/Toll-like receptor (IL-1/TLR) signaling cascades. These pathways are important for the host to control viral infections. In this report, we demonstrated that hepatitis C virus (HCV) depleted TRAF6 from its host cells through a post-translational mechanism. This depletion was independent of proteasomes, as it was not affected by the proteasome inhibitor MG132, but it was suppressed by bafilomycin A1, which led to the association of TRAF6 with autophagosomes...
September 28, 2016: Journal of Virology
Markus H Heim, Pierre-Yves Bochud, Jacob George
Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability...
October 2016: Journal of Hepatology
Jens Bukh
The discovery of hepatitis C virus (HCV) in 1989 permitted basic research to unravel critical components of a complex life cycle for this important human pathogen. HCV is a highly divergent group of viruses classified in 7 major genotypes and a great number of subtypes, and circulating in infected individuals as a continuously evolving quasispecies destined to escape host immune responses and applied antivirals. Despite the inability to culture patient viruses directly in the laboratory, efforts to define the infectious genome of HCV resulted in development of experimental recombinant in vivo and in vitro systems, including replicons and infectious cultures in human hepatoma cell lines...
October 2016: Journal of Hepatology
Clodoveo Ferri, Manuel Ramos-Casals, Anna Linda Zignego, Luca Arcaini, Dario Roccatello, Alessandro Antonelli, David Saadoun, Anne Claire Desbois, Marco Sebastiani, Milvia Casato, Peter Lamprecht, Alessandra Mangia, Athanasios G Tzioufas, Zobair M Younossi, Patrice Cacoub
Hepatitis C virus (HCV) infection is responsible for both hepatic and extra-hepatic disorders (HCV-EHDs); these latter are correlated on one hand clearly with HCV lymphotropism causing immune-system dysregulation as well as with viral oncogenic potential, and on the other hand probably with chronic inflammatory status causing cardio-metabolic complications as well as neurocognitive disturbances. The spectrum of HCV-EHDs ranges from mild or moderate manifestations, such as arthralgia, sicca syndrome, peripheral neuropathy, to severe, life-threatening complications, mainly vasculitis and neoplastic complications...
September 15, 2016: Autoimmunity Reviews
Dapeng Li, Markus von Schaewen, Xuesong Wang, Wanyin Tao, Yunfang Zhang, Li Li, Brigitte Heller, Gabriela Hrebikova, Qiang Deng, Alexander Ploss, Jin Zhong, Zhong Huang
: Hepatitis C virus (HCV) infection is a global health problem for which no vaccine is available. HCV has a highly heterogeneous RNA genome and can be classified into seven genotypes. Due to the high genetic and resultant antigenic variation among genotypes, inducing antibodies capable of neutralizing most of the HCV genotypes by experimental vaccination has been challenging. Previous efforts focused on priming humoral immune responses with recombinant HCV envelope E2 protein produced in mammalian cells...
September 14, 2016: Journal of Virology
Surasak Jittavisutthikul, Watee Seesuay, Jeeraphong Thanongsaksrikul, Kanyarat Thueng-In, Potjanee Srimanote, Rolf G Werner, Wanpen Chaicumpa
A safe and effective direct acting anti-hepatitis C virus (HCV) agent is still needed. In this study, human single chain variable fragments of antibody (scFvs) that bound to HCV NS3/4A protein were produced by phage display technology. The engineered scFvs were linked to nonaarginines (R9) for making them cell penetrable. HCV-RNA-transfected Huh7 cells treated with the transbodies produced from four different transformed E. coli clones had reduced HCV-RNA inside the cells and in the cell spent media, as well as fewer HCV foci in the cell monolayer compared to the transfected cells in culture medium alone...
2016: Frontiers in Immunology
Jonathan R Honegger, Dana Tedesco, Jennifer A Kohout, Mona R Prasad, Aryn A Price, Tera Lindquist, Samantha Ohmer, Melissa Moore-Clingenpeel, Arash Grakoui, Christopher M Walker
Chronic hepatitis C virus (HCV) infection is characterized by exhaustion of virus-specific T-cells and stable viremia. Pregnancy is an exception. Viremia gradually climbs during gestation but sometimes declines sharply in the months following delivery. Here, we demonstrated that postpartum HCV control was associated with enhanced virus-specific T-cell immunity. Women with viral load declines of at least 1 log10 between the third trimester and 3-mo postpartum exhibited HCV-specific T-cell responses of greater breadth (P = 0...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
J Pascual, A Royuela, A M Fernández, I Herrero, J F Delgado, A Solé, L Guirado, T Serrano, J de la Torre-Cisneros, A Moreno, E Cordero, R Gallego, C Lumbreras, J M Aguado
Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection...
September 7, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
M El-Bendary, M Neamatallah, G Esmat, E Kamel, H Elalfy, T Besheer, D Eldeib, A-H Eladl, M El-Setouhy, A-H El-Gilany, A El-Waseef
Hepatitis C infection is a global pandemic. HLA-DQB1 alleles are believed to have an effective role in immune response against HCV including susceptibility to or protection from this infection. The aim of this study was to investigate the contribution of HLA-DQB1 alleles in the outcome of HCV genotype-4 infection through a family-based association study. Egyptian families with HCV (324) were recruited for this study (324 index positive for RNA-HCV, 225 positive relatives representing chronic hepatitis C cases and 582 family members negative for HCV-RNA [control], 63 of whom spontaneously cleared the virus...
September 7, 2016: Journal of Viral Hepatitis
L B Dustin, B Bartolini, M R Capobianchi, M Pistello
Hepatitis C virus (HCV) is a major global health burden accounting for around 170 million chronic infections worldwide. Since its discovery, which dates back to about 30 years ago, many details of the viral genome organization and the astonishing genetic diversity have been unveiled but, owing to the difficulty of culturing HCV in vitro and obtaining fully susceptible yet immunocompetent in vivo models, we are still a long way from the full comprehension of viral life cycle, host cell pathways facilitating or counteracting infection, pathogenetic mechanisms in vivo, and host defences...
August 31, 2016: Clinical Microbiology and Infection
Luz M Medrano, Norma Rallón, Juan Berenguer, María A Jiménez-Sousa, Vicente Soriano, Teresa Aldámiz-Echevarria, Amanda Fernández-Rodríguez, Marcial García, Francisco Tejerina, Isidoro Martínez, José M Benito, Salvador Resino
BACKGROUND AND AIMS: TRIM5 and TRIM22 are restriction factors involved in innate immune response and exhibit anti-viral activity. Single nucleotide polymorphisms (SNPs) at TRIM5 and TRIM22 genes have shown to influence several viral infections such as human immunodeficiency virus (HIV), hepatitis B, as well as measles and rubella vaccination. The aim of this study is to analyze whether TRIM5 and TRIM22 polymorphisms are associated with liver fibrosis inflammation-related biomarkers and response to pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/hepatitis C virus (HCV) coinfected patients...
2016: Journal of Translational Medicine
Shanshan Wang, Yongzhi Chen, Chunfeng Li, Yaoxing Wu, Lei Guo, Changwei Peng, Yueping Huang, Genhong Cheng, F Xiao-Feng Qin
Tripartite motif 14 (TRIM14) was reported to function as a mitochondrial signaling adaptor in mediating innate immune responses. However, the involvement of TRIM14 in host defense against viral infection and molecular mechanisms remain unclear. Here, we demonstrated that enforced expression of TRIM14 could potently inhibit the infection and replication of HCV in hepatocytes, whereas TRIM14 knockout cells became more susceptible to HCV infection. Interestingly, further experiments revealed that such anti-HCV activity was independent of activating the NF-κB or interferon pathways but required the C-terminal SPRY domain of no signaling capacity...
2016: Scientific Reports
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