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HCV immunity

Yanan Zhao, Xuezhi Cao, Mingzhe Guo, Xuesong Wang, Tao Yu, Liqing Ye, Lin Han, Lei Hei, Wanyin Tao, Yimin Tong, Yongfen Xu, Jin Zhong
Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV can be sensed by host innate immunity to induce expression of interferons (IFNs) and a number of antiviral effectors. In this study, we found HCV infection induced the expression of Neuralized E3 Ubiquitin Protein Ligase 3 (NEURL3), a putative E3 ligase, in a manner that requires the involvement of innate immune sensing but is independent of the IFN action. Furthermore, we showed that NEURL3 inhibited HCV infection, while had little effect on other RNA viruses including zika virus, dengue virus and vesicular stomatitis virus...
August 15, 2018: Journal of Virology
Yuki Inada, Eishiro Mizukoshi, Takuya Seike, Toshikatsu Tamai, Noriho Iida, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Kazumi Fushimi, Taro Yamashita, Masao Honda, Shuichi Kaneko
Host antitumor immune responses may be different between hepatocellular carcinoma (HCC) caused by metabolic disorders and HCC associated with hepatitis virus infection. In this study, we examined the immune response of tumor-associated antigen (TAA)-specific T cells and immune cell profile in HCC patients separated by cause. Thirty two patients with HBV-related HCC, 42 patients with HCV-related HCC, and 18 patients with non-alcoholic steatohepatitis (NASH)-related HCC were analyzed. The frequencies of TAA-specific T cells, the expression levels of surface markers on each immune cell and the expression of each TAA in HCC tissue were measured...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ratna B Ray, Ranjit Ray
Chronic hepatitis C virus (HCV) infection associated liver disease is a global health problem. HCV often causes silent disease, and eventually progresses to end stage liver disease. HCV infects hepatocytes, however initial manifestation of liver disease is mostly displayed in hepatic stellate cells causing fibrosis/cirrhosis, and believed to be occurring from inflammation in the liver. It is still unclear why HCV is not spontaneously cleared from infected liver in the majority of individuals and develops chronic infection with progressive liver disease...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Carla Eller, Laura Heydmann, Che C Colpitts, Eloi R Verrier, Catherine Schuster, Thomas F Baumert
Chronic hepatitis B, C and D virus (HBV, HCV and HDV) infections are a major cause of liver disease and cancer worldwide. Despite employing distinct replication strategies, the three viruses are exclusively hepatotropic, and therefore depend on hepatocyte-specific host factors. The sodium taurocholate co-transporting polypeptide (NTCP), a transmembrane protein highly expressed in human hepatocytes that mediates the transport of bile acids, plays a key role in HBV and HDV entry into hepatocytes. Recently, NTCP has been shown to modulate HCV infection of hepatocytes by regulating innate antiviral immune responses in the liver...
August 10, 2018: Cellular and Molecular Life Sciences: CMLS
María Q Marín, Patricia Pérez, Carmen E Gómez, Carlos Óscar S Sorzano, Mariano Esteban, Juan García-Arriaza
Hepatitis C virus (HCV) represents a major global health problem for which a vaccine is not available. Modified vaccinia virus Ankara (MVA)-HCV is a unique HCV vaccine candidate based in the modified vaccinia virus Ankara (MVA) vector expressing the nearly full-length genome of HCV genotype 1a that elicits CD8⁺ T-cell responses in mice. With the aim to improve the immune response of MVA-HCV and because of the importance of interferon (IFN) in HCV infection, we deleted in MVA-HCV the vaccinia virus (VACV) C6L gene, encoding an inhibitor of IFN-β that prevents activation of the interferon regulatory factors 3 and 7 (IRF3 and IRF7)...
August 8, 2018: Viruses
Lídia Teixeira, Cristina Fonseca, Sandra Sousa, Filipe Vinagre, Ana Cordeiro, Pedro Gonçalves, Maria José Santos, José Canas da Silva
Hepatitis C virus (HCV) infection is a major public health problem. Because Tumour Necrosis Factor (TNF) seems to have an important role in immune response to HCV infection, suppression by TNFi (TNF inhibitors) may pose a potential worsening of chronic HCV infection. We report our experience with 3 cases of patients with chronic HCV infection and advanced liver disease, with different Rheumatic diseases, treated with a TNFi, etanercept (ETN), for a period ranging from 4 months to 4 years without hepatitis C treatment and, in two of them, concomitant therapy with direct-acting antiviral agents (DAA) and afterwards...
April 2018: Acta Reumatológica Portuguesa
Christine Chan, Thomas Schiano, Eliana Agudelo, John Paul Haydek, Maarouf Hoteit, Marcela P Laurito, John P Norvell, Norah Terrault, Elizabeth C Verna, Amy Yang, Josh Levitsky
Interferon treatment of hepatitis C virus (HCV) infection after liver transplantation (LT) can result in immune-mediated graft dysfunction (IGD). The occurrence of, risk factors for and outcomes of IGD with direct-acting antiviral (DAA) therapy have not been reported. We conducted a multicenter study of HCV+ LT recipients who did or did not develop DAA-IGD (1 case: 2 controls - 33 vs. 66). Among all treated between 2014-16, DAA-IGD occurred in 3.4% (33/978). IGD occurred only after treatment completion (113 ± 84 days)...
August 3, 2018: American Journal of Transplantation
Kun Wei, Ben-Chun Jiang, Jing-Hui Guan, Dong-Na Zhang, Meng-Xuan Zhang, Jun-Long Wu, Guang-Ze Zhu
Direct-acting antivirals (DAAs) not only rapidly inhibited hepatitis C virus (HCV) replication but also modulated innate and adaptive immune response in chronic hepatitis C patients. However, the regulatory activity of DAAs to Toll-like receptor 2 (TLR2) stimulation on CD4+ CD25+ CD127dim/- regulatory T cells (Tregs) and T helper (Th) 17 cells was not completely understood. In the present study, a total of 23 patients with chronic HCV genotype 1b infection were enrolled, and blood samples were collected at baseline (treatment naive), end of therapy (EOT), and 12 weeks after EOT (SVR12) with daclatasvir plus asunaprevir therapy...
August 1, 2018: Viral Immunology
Valéria Maciel Cordeiro, Bruno César Teodoro Martins, Sheila Araujo Teles, Regina Maria Bringel Martins, Karla Prado de Souza Cruvinel, Márcia Alves Dias de Matos, Jonio Arruda Luz, Regiane Aparecida Dos Santos Soares Barreto, Juliana Araujo Teles, Nathália Carneiro Santos, Karlla Antonieta Amorim Caetano, Megmar Aparecida Dos Santos Carneiro
Infection control measures have been responsible for a decline in the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in hemodialysis patients. In Brazil, these measures have been in place since 1996. The aim of this study was to evaluate the current HBV and HCV epidemiology among hemodialysis patients in the State of Tocantins comparing them with those found 14 years ago. There was a significant decline in hepatitis B surface antigen (HBsAg) and anti-HCV prevalence from 4% and 13% in 2001 to 0...
July 30, 2018: Revista do Instituto de Medicina Tropical de São Paulo
(no author information available yet)
Liver cancer is one of the most common cancers in China. The major risk factors are chronic infections of hepatitis B virus (HBV), hepatitis C virus (HCV), high exposure to aflatoxins. In addition, exposure to cyanotoxins and some preventable health behaviors are also recognized to contribute to liver cancer development. To relieve the disease burden, primary prevention of etiological interventions is an important strategy. Based on the liver cancer epidemiology in China and the effective evidences and results from the etiological interventions conduced in Chinese population domestically, the following strategies are recommended in the "Strategies of primary prevention of liver cancer: Expert Consensus (2018)" to promote the effective prevention of liver cancer in general population...
July 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Lize Cuypers, Ana Belén Pérez, Natalia Chueca, Teresa Aldamiz-Echevarría, Juan Carlos Alados, Ana María Martínez-Sapiña, Dolores Merino, Juan Antonio Pineda, Francisco Téllez, Nuria Espinosa, Javier Salméron, Antonio Rivero-Juarez, María Jesús Vivancos, Víctor Hontañón, Anne-Mieke Vandamme, Féderico García
Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12...
2018: PloS One
Sebastian Lunemann, Anja Schöbel, Janine Kah, Pia Fittje, Angelique Hölzemer, Annika E Langeneckert, Leonard Hess, Tobias Poch, Gloria Martrus, Wilfredo F Garcia-Beltran, Christian Körner, Anne-Rose Ziegler, Laura Richert, Karl J Oldhafer, Julian Schulze Zur Wiesch, Christoph Schramm, Maura Dandri, Eva Herker, Marcus Altfeld
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer (NK) cells. Binding of KIR3DS1 to its recently discovered ligand, HLA-F, activates NK cells and has been associated with resolution of hepatitis C virus (HCV) infection. We investigated the mechanisms by which KIR3DS1 contributes to the antiviral immune response. Using cell culture systems, mice with humanized livers , and primary liver tissue from HCV-infected individuals, we found that the KIR3DS1 ligand HLA-F is upregulated on HCV-infected cells, and that interactions between KIR3DS1 and HLA-F contribute to NK cell-mediated control of HCV...
July 19, 2018: Gastroenterology
Houssein H Ayoub, Hiam Chemaitelly, Ryosuke Omori, Laith J Abu-Raddad
OBJECTIVES: Hepatitis C virus (HCV) clearance rate (fclearance ) is defined as the proportion of infected persons who will spontaneously clear their infection after acute infection. We aimed to estimate fclearance using a novel approach that avoids limitations in existing estimates, and to clarify the link between fclearance and HCV viremic rate-the latter being the proportion of RNA positivity among those antibody positive. METHODS: A mathematical model was developed to describe HCV transmission...
July 18, 2018: International Journal of Infectious Diseases: IJID
Asmaa Nafady, Hanaa Nafady-Hego, Nadia M Abdelwahab, Radwa H N Eltellawy, Nagla H Abu Faddan
BACKGROUND: Hepatitis C virus (HCV)-specific immune response is believed to play a crucial role in viral clearance. There is, nevertheless, no reliable parameter to monitor this immune response or predict chronic HCV infection development. METHOD: An observational case-control study was performed to identify such parameters, peripheral blood mononuclear cells from 57 children with chronic HCV were systemically phenotyped, and the serum level of Interferon gamma and interleukin (IL) -17 was measured...
July 19, 2018: European Journal of Clinical Investigation
Francesca Tucci, Valeria Calbi, Federica Barzaghi, Maddalena Migliavacca, Francesca Ferrua, Maria Ester Bernardo, Daniele Canarutto, Giulia Consiglieri, Salvatore Recupero, Francesco Calzatini, Michela Gabaldo, Caterina Lucano, Miriam Casiraghi, Silvia Darin, Francesca Dionisio, Sarah Marktel, Enza Cestone, Renato Finazzi, Giorgina Mieli-Vergani, Enzo Boeri, Jonathan Appleby, Dalia Abd Elaziz, Fabio Ciceri, Alessandro Aiuti, Maria Pia Cicalese
Patients with inborn error diseases can be candidates for autologous haematopoietic stem cells (HSC) gene therapies (GT) but may require negative viral screening, including Hepatitis C (HCV), to allow HSC manipulation in Good Manufacturing Practices areas. In case of HCV positivity, patients might be excluded from life-saving treatments. As HCV antibodies could be negative in young infant immunodeficient patients due to their immature/impaired immune system, or positive due to maternal-fetal antibody transmission, the risk is usually also evaluated on the basis of the HCV-RNA...
July 16, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Naglaa H Shoukry
The development of vaccines that protect against persistent hepatitis C virus (HCV) infection remain a public health priority. The broad use of highly effective direct-acting antivirals (DAAs) is unlikely to achieve HCV elimination without vaccines that can limit viral transmission. Two vaccines targeting either the antibody or the T cell response are currently in preclinical or clinical trials. Next-generation vaccines will likely involve a combination of these two strategies. This review summarizes the state of knowledge about the immune protective role of HCV-specific antibodies and T cells and the current vaccine strategies...
2018: Frontiers in Immunology
Vishnu Venugopal, Pranesh Padmanabhan, Rubesh Raja, Narendra M Dixit
Direct-acting antiviral agents (DAAs) for hepatitis C treatment tend to fare better in individuals who are also likely to respond well to interferon-alpha (IFN), a surprising correlation given that DAAs target specific viral proteins whereas IFN triggers a generic antiviral immune response. Here, we posit a causal relationship between IFN-responsiveness and DAA treatment outcome. IFN-responsiveness restricts viral replication, which would prevent the growth of viral variants resistant to DAAs and improve treatment outcome...
July 2018: PLoS Computational Biology
Marian Major, Alexander Gutfraind, Louis Shekhtman, Qingwen Cui, Alla Kachko, Scott J Cotler, Behzad Hajarizadeh, Rachel Sacks-Davis, Kimberly Page, Basmattee Boodram, Harel Dahari
The major route of hepatitis C virus (HCV) transmission in the United States is injection drug use. We hypothesized that if an HCV vaccine were available, vaccination could affect HCV transmission among people who inject drugs by reducing HCV titers after viral exposure without necessarily achieving sterilizing immunity. To investigate this possibility, we developed a mathematical model to determine transmission probabilities relative to the HCV RNA titers of needle/syringe-sharing donors. We simulated sharing of two types of syringes fitted with needles that retain either large or small amounts of fluid after expulsion...
July 11, 2018: Science Translational Medicine
Y Y Ye, H Chen, Y Yan, L Chen, W X Huang
Objective: To study the efficacy of vitamin E-loaded lipid nanoparticles (VE-DC) in the mouse model to target small interfering RNA (siRNA) for inhibition of hepatitis C virus(HCV) core protein expression. Methods: A high-pressure hydrodynamic method was adopted to construct an animal model of liver-specific expression to inject the plasmid containing HCV core protein into mice tail vein. Western blotting and immunofluorescence techniques were used to evaluote the liver targeting property of VE - DC/siRNA nanoparticles and the effectiveness to repress HCV Core expression...
May 20, 2018: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Susanna Naggie, Marzena Swiderska-Syn, Steve Choi, Sam Lusk, Audrey Lan, Guido Ferrari, Wing-Kin Syn, Cynthia D Guy, Anna Mae Diehl
Liver disease is a leading cause of HIV-related mortality. Hepatitis C virus (HCV)-related fibrogenesis is accelerated in the setting of HIV coinfection, yet the mechanisms underlying this aggressive pathogenesis are unclear. We identified formalin-fixed paraffin-embedded liver tissue for HIV-infected patients, HCV-infected patients, HIV/HCV-coinfected patients, and controls at Duke University Medical Center. De-identified sections were stained for markers against the wound repair Hedgehog (Hh) pathway, resident T-lymphocytes, and immune activation and cellular aging...
July 2018: Open Forum Infectious Diseases
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