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Immune response to HCV

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
John L M Law, Michael Logan, Jason Wong, Juthika Kundu, Darren Hockman, Amir Landi, Chao Chen, Kevin Crawford, Mark Wininger, Janelle Johnson, Catalina Mesa Prince, Elzbieta Dudek, Ninad Mehta, D Lorne Tyrrell, Michael Houghton
Current evidence supports a protective role for virus neutralizing antibodies in immunity against HCV infection. Many cross-neutralizing monoclonal antibodies have been identified. These antibodies have been shown to protect or clear infection in animal models. Previous clinical trials have shown a gpE1/gpE2 vaccine can induce antibodies that neutralize the in vitro infectivity of all the major HCVcc genotypes around the world. However, cross-neutralization appeared to favour certain genotypes with significant but lower neutralization against others...
March 14, 2018: Journal of Virology
Oliver Grünvogel, Ombretta Colasanti, Ji-Young Lee, Volker Klöss, Sandrine Belouzard, Anna Reustle, Katharina Esser-Nobis, Jasper Hesebeck-Brinckmann, Pascal Mutz, Katrin Hoffmann, Arianeb Mehrabi, Ronald Koschny, Florian W R Vondran, Daniel Gotthardt, Paul Schnitzler, Christoph Neumann-Haefelin, Robert Thimme, Marco Binder, Ralf Bartenschlager, Jean Dubuisson, Alexander H Dalpke, Volker Lohmann
BACKGROUND & AIMS: Hepatitis C virus (HCV) infections most often result in chronic outcomes, although the virus constantly produces replication intermediates, in particular double-stranded RNA (dsRNA), representing potent inducers of innate immunity. We aimed to characterize the fate of HCV dsRNA in hepatocyte cultures to identify mechanisms contributing to viral persistence in presence of an active innate immune response. METHODS: We analyzed hepatocyte-based culture models for HCV for induction of innate immunity, secretion of virus positive- or negative-strand RNA, and viral replication using different quantification methods and microscopy techniques...
March 10, 2018: Gastroenterology
Ghaly M F, Fadia M Attia, Rania M Saleh, Heba M, Maha Anani
IL-22 plays a vital role in improving hepatic damage by targeting hepatocytes that express high levels of IL-22 receptor1. IP-10 is a chemokine that recruit mononuclear cells to liver parenchyma and improves the host immune response against hepatitis C virus. The study targeted 27 patients with chronic HCV who received pegylated Interferon and Ribavirin. IL-22 and IP-10 serum levels were measured by Elisa. The level of the serum IL-22 is higher in HCV patients groups receiving the antiviral treatment compared to control group and its levels significantly increased with response to treatment...
June 2017: Egyptian Journal of Immunology
Saba Valadkhan, Puri Fortes
The interferon (IFN) response is a critical component of the innate immunity antiviral pathways in mammalians. IFN signaling results in increased expression of cellular factors that block key steps in the viral replication cycle. Many IFN-induced antiviral factors act through decreasing viral entry, replication, transcription, translation, packaging and release. However, these effects are also deleterious for the viability of the cell, which necessitates a tight control over the magnitude and duration of the IFN response...
2018: Frontiers in Microbiology
Takao Wanatabe, Takeshi Imamura, Yoichi Hiasa
Double-stranded (ds) RNA-dependent protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. It was initially identified as an innate immune anti-viral protein induced by interferon (IFN) and activated by dsRNA. PKR is recognized as a key executor of the antiviral host defense. Moreover, it contributes to inflammation and immune regulation through several signaling pathways. In addition to IFN and dsRNA, PKR is activated by multiple stimuli and regulates various signaling pathways including the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells pathways...
February 25, 2018: Cancer Science
Jun Gu, Joshua Hardy, Irene Boo, Patricia Vietheer, Kathleen McCaffrey, Yousef Alhammad, Abha Chopra, Silvana Gaudieri, Pantelis Poumbourios, Fasséli Coulibaly, Heidi E Drummer
The Hepatitis C Virus (HCV) E2 glycoprotein is a major target of the neutralizing antibody response with multiple type-specific and broadly neutralizing antibody epitopes identified. The 412-423 region can generate broadly neutralizing antibodies (bnNAbs) that block interaction with the cell surface receptor CD81, with activity towards multiple HCV genotypes. In this study we reveal the structure of the rodent MAb24 with an extensive contact area towards a peptide spanning the 412-423 region. The crystal structure of the MAb24-peptide 412-423 complex reveals the paratope bound to a peptide hairpin, highly similar to that observed with human MAb HCV1, but with a different angle of approach...
February 21, 2018: Journal of Virology
Zhengang Shan, Jieting Huang, Qiao Liao, Ke Huang, Min Wang, Ru Xu, Xi Tang, Weiyun Zhang, Kenrad Nelson, Yongshui Fu, Chengyao Li, Xia Rong
BACKGROUND: Natural killer (NK) cells are critical components in innate immune response to viral infection. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating the balance of activation or inhibitory function of NK cells. However, the association of KIRs with the spontaneous clearance of hepatitis C virus (HCV) remains unclear in the Chinese population. STUDY DESIGN AND METHODS: A total of 407 HCV-seropositive voluntary blood donors were recruited, including 203 with spontaneous viral clearance and 204 with chronic infection...
February 15, 2018: Transfusion
Young-Chan Kwon, Keith Meyer, Guangyong Peng, Soumya Chatterjee, Daniel F Hoft, Ranjit Ray
A comprehensive strategy to control HCV infection needs a vaccine. Our phase I study with recombinant HCV E1/E2 EnvGPs as a candidate vaccine did not induce a strong immune response in volunteers. We analyzed the interactions of HCV EnvGPs with human monocyte derived macrophages as antigen presenting cells. HCV E2 induced immune regulatory cytokine IL-10 and sCD163 protein expression in macrophages from 7 of 9 blood donors tested. Further, HCV E2 enhanced Stat3 and suppressed Stat1 activation, reflecting macrophage polarization towards M2 phenotype...
February 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yumiko Nagao, Kazunori Nakasone, Tatsuji Maeshiro, Nao Nishida, Kanae Kimura, Yuji Kawahigashi, Yasuhito Tanaka, Michio Sata
Hepatitis C virus (HCV) infection is frequently associated with various extrahepatic manifestations, such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP) is one such extrahepatic manifestation of HCV infection. Recently, direct-acting antivirals (DAA) have proved to be highly effective and safe for the eradication of HCV. Herein, we report a case of OLP accompanied by HCV-related hepatocellular carcinoma (HCC) that disappeared after liver transplantation and achievement of sustained virological response following interferon (IFN)-free treatment with ledipasvir (LDV) and sofosbuvir (SOF)...
September 2017: Case Reports in Gastroenterology
Ahmad Karkhah, Mostafa Javanian, Soheil Ebrahimpour
Two hepatotropic viruses hepatitis C virus (HCV) and hepatitis B virus (HBV) have been considered as the main cause of chronic viral infections. In addition, human immunodeficiency virus (HIV) attacks the immune system by eradication of some white blood cell (T-helper cell). The role of Tregs in HCV, HBV and HIV infections ranges from suppressing antiviral T cell responses to protecting tissues as liver and immune cells from immune mediated injury. In this review, we discuss the influence of regulatory T cells in immunopathology of specific viral infections including HCV, HBV and HIV by focusing on targeting Tregs as novel approach in vaccinology against viral infections...
January 29, 2018: Infection, Genetics and Evolution
Pascal Mutz, Philippe Metz, Florian A Lempp, Silke Bender, Bingqian Qu, Katrin Schöneweis, Stefan Seitz, Thomas Tu, Agnese Restuccia, Jamie Frankish, Christopher Dächert, Benjamin Schusser, Ronald Koschny, Georgios Polychronidis, Peter Schemmer, Katrin Hoffmann, Thomas F Baumert, Marco Binder, Stephan Urban, Ralf Bartenschlager
BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy whereas HBV infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in co-infected cells. We investigated interactions between HBV and the IFN-mediated immune response using HepaRG cells and primary human hepatocytes (PHHs). We analyzed the effects of HBV on HCV replication, and vice versa, at the single-cell level...
January 31, 2018: Gastroenterology
Anita Kothapalli, Muhammad A Khattak
Anti-PD-1 monoclonal antibodies have shown durable long-term survival benefit in patients with metastatic melanoma. Limited evidence exists on the safety and efficacy of PD-1 inhibitors in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections as these patients have traditionally been excluded from clinical trials because of a theoretical risk of immune reconstitution inflammatory syndrome. We aim to determine the safety and efficacy of treatment with PD-1 inhibitors in seven patients with HBV/HCV infection and concurrent metastatic melanoma or non-small-cell lung cancer (NSCLC)...
February 5, 2018: Melanoma Research
Nghiem Xuan Hoan, Hoang Van Tong, Le Huu Song, Christian G Meyer, Thirumalaisamy P Velavan
The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses (HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide...
January 28, 2018: World Journal of Gastroenterology: WJG
Manu Asthana, Sushil Kumar Sahu, Amit Kumar, Suchitra Mohanty, Sudipta Chakrabarti, Piyanki Das, Nabanita Roy Chattopadhya, Koustav Chatterjee, Shivaram Prasad Singh, Shanmugam Rajasubramaniam, Tathagata Choudhuri
Interleukin-28B (IL28B) locus on a human chromosomal region 19q13 is responsible for immune protection against viruses. IL28B in hepatitis C virus (HCV) infection determines the fate of infection towards causing spontaneous clearance or chronic liver infection. Choice of treatment in chronic hepatitis C infection includes use of direct acting antivirals, pegylated-interferon (PEG-IFN) or ribavirin (RBV) therapy. Interferon free regimens are also suggested to be useful in drug resistant patients. Genome-wide association studies (GWAS), comprehensive meta-analysis and independent case-control studies in different ethnic populations have demonstrated association between certain Il-28B polymorphisms and its effect on the response to PEG-IFN-RBV therapy in HCV patients...
January 28, 2018: Current Drug Metabolism
Laura Santangelo, Veronica Bordoni, Claudia Montaldo, Eleonora Cimini, Alessandra Zingoni, Cecilia Battistelli, Gianpiero D'Offizi, Maria R Capobianchi, Angela Santoni, Marco Tripodi, Chiara Agrati
BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is known to cause major alterations in the cross-talk between hepatic and immune cells thus contributing to the liver disease pathogenesis. Extracellular vesicles have been proved to act as major players in cell-cell communication, and their cargo changes in relation to pathophysiological states. The aim of this study was to evaluate the effects of chronic HCV infection and direct-acting antivirals (DAA) on exosome-delivered microRNAs and on their ability to modulate the innate immune response...
January 22, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Pinar Mesci, Angela Macia, Spencer M Moore, Sergey A Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R Fernandes, Nicole A Suarez, Matthew J Kolar, Sandro Montefusco, Scott C Rosenberg, Roberto H Herai, Fernanda R Cugola, Fabiele B Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D Momper, Jair L Siqueira-Neto, Kevin D Corbett, Patricia C B Beltrão-Braga, Alexey V Terskikh, Alysson R Muotri
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs...
January 19, 2018: Scientific Reports
Stanislas Pol, Anaïs Vallet-Pichard, Olivier Hermine
Infectious agents, such as HCV, account for ∼15% of human cancers. HCV infects not only hepatocytes but also extrahepatic cells. Chronic HCV infection can induce chronic inflammation with qualitative and quantitative alterations of the immune repertoire and tissue microenvironment, which could induce various neoplasias. Epidemiological studies and meta-analyses suggest an increased rate of extrahepatic cancers in patients with chronic HCV infection along with a higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin lymphoma (NHL), highlighting the need to screen for HCV infection in patients with these cancers...
January 17, 2018: Nature Reviews. Gastroenterology & Hepatology
K Young, K Haq, S MacLean, R Dudani, S M Elahi, R Gilbert, R Weeratna, L Krishnan
Hepatitis C virus (HCV) chronically infects 2-3% of the world's population, causing liver disease and cancer with prolonged infection. The narrow host range of the virus, being restricted largely to human hepatocytes, has made the development of a relevant infection and reliable model to evaluate the efficacy of vaccines a challenge. We have developed a novel approach to accomplish this by generating a murine hepatoma cell line stably expressing non-structural HCV antigens which can be used in vitro or in vivo to test HCV vaccine efficacies...
January 6, 2018: Journal of Viral Hepatitis
Pratichi Singh, Febin Prabhu Dass J
Hepatitis C virus infection causes chronic liver disease that leads to cancer-related mortality. Presently around 30% of the HCV (infected) affected population get rid of the infection through spontaneous disease clearance. This phenomenon is conducted by a set of reported immune candidate genes. Hence, this study focuses only on these immune-response related genes with aid of network approach, where the idea is to disseminate the network for better understanding of key functional genes and their transcription control activity...
January 8, 2018: Cell Biochemistry and Biophysics
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