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Immune response to HCV

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https://www.readbyqxmd.com/read/28228595/hepatitis-c-virus-specific-t-cell-receptor-mrna-engineered-human-t-cells-impact-of-antigen-specificity-on-functional-properties
#1
Anangi Balasiddaiah, Haleh Davanian, Soo Aleman, Anna Pasetto, Lars Frelin, Matti Sällberg, Volker Lohmann, Sarene Koh, Antonio Bertoletti, Margaret Chen
Therapy with genetically modified autologous T cells has shown great promise in cancer therapy. For an efficient control of hepatitis C virus (HCV) infection, cytotoxic T cells (CTL) are pivotal but persistence of activated T cells may lead to liver toxicity. Here, anti-HCV T cell receptors (TCRs) recognising the HCV non-structural (NS) NS3 or NS5 viral peptide target were examined by mRNA transfection of human peripheral blood lymphocytes (PBL) derived from healthy donors as well as chronically infected HCV patients...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28225833/influence-of-hla-class-i-hla-class-ii-and-kirs-on-vertical-transmission-and-chronicity-of-hepatitis-c-virus-in-children
#2
A Ruiz-Extremera, E J Pavón-Castillero, M Florido, P Muñoz de Rueda, J A Muñoz-Gámez, J Casado, A Carazo, R Quiles, S M Jiménez-Ruiz, A Gila, J D Luna, J León, J Salmerón
BACKGROUND & AIM: There is evidence that maternal viral load of HCV during delivery influences the risk for Mother-to-child transmission (MTCT), but this does not explain all cases. We study the role of the immunogenetic profile (HLA, KIRs and KIR-ligand binding) of mothers and children in HCV-MTCT and in chronicity in the children. METHODOLOGY: 79 HCV-RNA (+) mothers and their 98 children were included. 24 children were infected, becoming chronic in 8 cases and clearing in 16...
2017: PloS One
https://www.readbyqxmd.com/read/28218976/differential-expression-of-innate-immune-response-genes-in-clinical-phases-of-chronic-hepatitis-b-infection
#3
Sara Romani, Seyed Masoud Hosseini, Seyed Reza Mohebbi, Andre Boonstra, Afsaneh Sharifian
We investigated innate immune gene expression in clinical phases of Chronic Hepatitis B infection, including immune tolerant (IT); immune active (IA); inactive carrier (IC); and hepatitis B e antigen (HBeAg)-negative phases, as well as healthy controls. Expression levels of interferon types I, II, and III, their receptor subunits, IRFs, TLRs and other IFN-induced genes in peripheral blood mononuclear cells were compared.Forty HBsAg-positive treatment-naïve subjects without co-infection with HIV, HCV or HDV were enrolled...
February 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28192188/hepatitis-c-virus-induced-nk-cell-activation-causes-metzincin-mediated-cd16-cleavage-and-impaired-antibody-dependent-cytotoxicity
#4
Barbara Oliviero, Stefania Mantovani, Stefania Varchetta, Dalila Mele, Giulia Grossi, Serena Ludovisi, Elisa Nuti, Armando Rossello, Mario U Mondelli
BACKGROUND & AIMS: The Fc receptor family for IgG type III (FcγRIII, CD16) is an activating receptor on natural killer (NK) cells and an essential mediator of antibody-dependent cellular cytotoxicity (ADCC). There is only limited information on its role during chronic hepatitis C virus (HCV) infection. We studied CD16 expression in relation to NK cell functional activity in HCV-infected patients and sought mechanistic insights into virus-induced modulation. METHODS: NK cell CD16 expression and activation status were evaluated ex vivo by flow cytometry in HCV-infected patients and healthy controls (HC) as well as in vitro after co-culture with HCV-infected Huh 7...
February 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28174739/increased-mitochondrial-genetic-diversity-in-persons-infected-with-hepatitis-c-virus
#5
David S Campo, Ha-Jung Roh, Brian L Pearlman, Daniel S Fierer, Sumathi Ramachandran, Gilberto Vaughan, Andrew Hinds, Zoya Dimitrova, Pavel Skums, Yury Khudyakov
BACKGROUND & AIMS: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. METHODS: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28170421/comprehensive-mapping-of-antigen-specific-t-cell-responses-in-hepatitis-c-virus-infected-patients-with-or-without-spontaneous-viral-clearance
#6
Chao Zhang, Rui Hua, Yuanyuan Cui, Shasha Wang, Hongqing Yan, Dongmei Li, Yonghong Zhang, Zhengkun Tu, Pei Hao, Xinyue Chen, Jin Zhong, Junqi Niu, Xia Jin
Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/28164561/frequency-of-foxp3-regulatory-t-cells-in-the-blood-of-chronic-hepatitis-c-patients-with-immune-mediated-skin-manifestations-relationship-to-hepatic-condition-and-viral-load
#7
Carmen Farid, Wafaa El Sheikh, Rania Swelem, Engy El-Ghitany
BACKGROUND: Chronic hepatitis C (CHC) infection causes a wide range of immune mediated hepatic and extrahepatic manifestations. Cutaneous manifestations constitute a major portion of the latter group. Host immune response to the virus - particularly regulatory T lymphocytes - is important in determining the outcome of the infection and the possibility of extrahepatic manifestations. The present study aims to investigate the relationship between immune-mediated cutaneous manifestations of CHC infection and the frequency of CD4+CD25 high FOXP3+ T regulatory lymphocytes...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28164540/level-of-human-antibodies-targeting-hcv-e1-e2-peptides-and-spontaneous-clearance-of-hcv-in-blood-donors
#8
Ashraf A Tabll, Eman A Salem, Yasmine S El-Abd, Reem M El-Shenawy, Amr Saad, Sanaa O Abdallah, Reham M Dawood, Mostafa K El-Awady
BACKGROUND: Hepatitis C virus (HCV) is a major health problem worldwide particularly in Egypt. The humoral immune response has an important function in the control of HCV infection. The aim of this study was to investigate the role of neutralizing antibodies in Hepatitis C Virus (HCV) clearance in infected individuals. METHODS: This study was carried out on apparently healthy blood donors (n = 200). Detectable HCV antibodies were assessed by commercial ELISA and specific human immunoglobulins targeting peptides derived from HCV E1/E2 glycoproteins were measured in donors' blood using an in house optimized ELISA...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28159892/systematic-identification-of-anti-interferon-function-on-hepatitis-c-virus-genome-reveals-p7-as-an-immune-evasion-protein
#9
Hangfei Qi, Virginia Chu, Nicholas C Wu, Zugen Chen, Shawna Truong, Gurpreet Brar, Sheng-Yao Su, Yushen Du, Vaithilingaraja Arumugaswami, C Anders Olson, Shu-Hua Chen, Chung-Yen Lin, Ting-Ting Wu, Ren Sun
Hepatitis C virus (HCV) encodes mechanisms to evade the multilayered antiviral actions of the host immune system. Great progress has been made in elucidating the strategies HCV employs to down-regulate interferon (IFN) production, impede IFN signaling transduction, and impair IFN-stimulated gene (ISG) expression. However, there is a limited understanding of the mechanisms governing how viral proteins counteract the antiviral functions of downstream IFN effectors due to the lack of an efficient approach to identify such interactions systematically...
February 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28157396/notch-signaling-modulates-the-balance-of-regulatory-t-cells-and-t-helper-17-cells-in-patients-with-chronic-hepatitis-c
#10
Lei Qin, Yan-Cai Zhou, Hong-Jie Wu, Ya Zhuo, Yan-Ping Wang, Chang-Yun Si, Yong-Mei Qin
The imbalance of regulatory T cells (Tregs) and T helper 17 (Th17) cells contributes to the persistent hepatitis C virus (HCV) infection. However, modulatory factors associated with Tregs-Th17 balance were not fully elucidated. A recent study demonstrated an immunoregulatory strategy by inactivation of Notch signaling to reverse the disequilibrium of Tregs-Th17 cells in immune thrombocytopenia. Thus, the aim of this study was to assess the effect of Notch signaling in regulating the functions of Tregs and Th17 cells in chronic hepatitis C...
February 3, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28149647/hepatitis-c-and-kidney-disease-a-narrative-review
#11
REVIEW
Rashad S Barsoum, Emad A William, Soha S Khalil
Hepatitis-C (HCV) infection can induce kidney injury, mostly due to formation of immune-complexes and cryoglobulins, and possibly to a direct cytopathic effect. It may cause acute kidney injury (AKI) as a part of systemic vasculitis, and augments the risk of AKI due to other etiologies. It is responsible for mesangiocapillary or membranous glomerulonephritis, and accelerates the progression of chronic kidney disease due to other causes. HCV infection increases cardiovascular and liver-related mortality in patients on regular dialysis...
March 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28149646/vasculitic-syndromes-in-hepatitis-c-virus-a-review
#12
REVIEW
Gaafar Ragab, Mohamed A Hussein
Vasculitis is a remarkable presentation of the extrahepatic manifestations of HCV. According to the presence or absence of cryoglobulins it is subdivided into two main types: cryoglobulinemic vasculitis and non cryoglobulinemic vasculitis based on the attribution of vasculitis to serum cryoglobulins as a pathogenic factor. The attribution of cryoglobulinemia to HCV represents a success story in the history of immunology, microbiology, and clinical medicine. HCV can bind to and invade lymphocytes, consequently triggering an immune response through different mechanisms...
March 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28124616/comparison-of-hcv-core-and-coree1e2-virus-like-particles-generated-by-stably-transfected-leishmania-tarentolae-for-stimulation-of-th1-immune-responses-in-mice
#13
Azam Bolhassani, Noushin Davoudi, Elnaz Agi
Virus-like particles (VLPs) could be improved into successful immunogens as well as a potent delivery vehicle, but however, the current expression systems for VLPs production have some limitations. Recently, we developed a novel strategy to produce two HCV VLPs containing core or coreE1E2 proteins using stably transfected Leishmania tarentolae promastigotes. Then, BALB/c mice were injected by both viral like particles in different immunization strategies such as homologous DNA-, homologous VLP-, and heterologous DNA/ VLP-based immunizations...
January 25, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28114346/hepatitis-c-virus-induces-mdscs-like-monocytes-through-tlr2-pi3k-akt-stat3-signaling
#14
Naicui Zhai, Haijun Li, Hongxiao Song, Yang Yang, An Cui, Tianyang Li, Junqi Niu, Ian Nicholas Crispe, Lishan Su, Zhengkun Tu
BACKGROUND AND AIMS: Recent studies reveal the accumulation of myeloid derived suppressor cells (MDSCs) in human peripheral blood mononuclear cells (PBMCs) following HCV infection, which may facilitate and maintain HCV persistent infection. The mechanisms by which HCV induces MDSCs are poorly understood. In the present study, we investigated the mechanisms by which HCV induces MDSCs that lead to suppression of T cell proliferation and expansion of CD4+Foxp3+ regulatory T cells. METHODS: Purified monocytes from healthy donors were cultured with HCV core protein (HCVc) or cell culture-derived HCV virions (HCVcc), and characterized the phenotype and function of these monocytes by flow cytometry, quantitative PCR, ELISA and western blot assays...
2017: PloS One
https://www.readbyqxmd.com/read/28112593/oral-combination-vaccine-comprising-bifidobacterium-displaying-hepatitis-c-virus-nonstructural-protein-3-and-interferon-%C3%AE-induces-strong-cellular-immunity-specific-to-nonstructural-protein-3-in-mice
#15
Koichi Kitagawa, Chika Omoto, Tsugumi Oda, Ayame Araki, Hiroki Saito, Katsumi Shigemura, Takane Katayama, Hak Hotta, Toshiro Shirakawa
We previously generated an oral hepatitis C virus (HCV) vaccine using Bifidobacterium displaying the HCV nonstructural protein 3 (NS3) polypeptide. NS3-specific cellular immunity is important for viral clearance and recovery from HCV infection. In this study, we enhanced the cellular immune responses induced by our oral HCV vaccine, Bifidobacterium longum 2165 (B. longum 2165), by combining interferon-α (IFN-α) as an adjuvant with the vaccine in a mouse experimental model. IFN-α is a widely used cytokine meeting the standard of care (SOC) for HCV infection and plays various immunoregulatory roles...
January 23, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28107583/chronic-hepatitis-c-and-chronic-kidney-disease-advances-limitations-and-unchartered-territories
#16
Manuel Mendizabal, K Rajender Reddy
Over the past few years, treatment options for chronic hepatitis C virus (HCV) infection have evolved dramatically. The current approved interferon-free direct-acting antiviral (DAA) regimens have been shown to be safe and effective with sustained virologic response (SVR) rates of >90% in most patients. Unique issues yet remain such as the challenges in patients with impaired renal function or decompensated cirrhosis. Patients with stage 4-5 chronic kidney disease (CKD) have a higher prevalence of HCV infection compared with the general population...
January 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28107512/nonstructural-5a-protein-of-hepatitis-c-virus-interferes-with-toll-like-receptor-signaling-and-suppresses-the-interferon-response-in-mouse-liver
#17
Takeya Tsutsumi, Kazuya Okushin, Kenichiro Enooku, Hidetaka Fujinaga, Kyoji Moriya, Hiroshi Yotsuyanagi, Hideki Aizaki, Tetsuro Suzuki, Yoshiharu Matsuura, Kazuhiko Koike
The hepatitis C virus nonstructural protein NS5A is involved in resistance to the host immune response, as well as the viral lifecycle such as replication and maturation. Here, we established transgenic mice expressing NS5A protein in the liver and examined innate immune responses against lipopolysaccharide (LPS) in vivo. Intrahepatic gene expression levels of cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ were significantly suppressed after LPS injection in the transgenic mouse liver...
2017: PloS One
https://www.readbyqxmd.com/read/28104239/cd8-t-cells-of-chronic-hcv-infected-patients-express-multiple-negative-immune-checkpoints-following-stimulation-with-hcv-peptides
#18
Muttiah Barathan, Rosmawati Mohamed, Jamuna Vadivelu, Li Yen Chang, Ramachandran Vignesh, Jayalakshmi Krishnan, Panneer Sigamani, Alireza Saeidi, M Ravishankar Ram, Vijayakumar Velu, Marie Larsson, Esaki M Shankar
Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA)...
December 16, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/28092420/immune-modulation-by-the-hepatitis-c-virus-core-protein
#19
Cecilia Fernández-Ponce, Juan Pedro Muñoz-Miranda, Mikel M Arbulo-Echevarria, Rocío Litrán, Enrique Aguado, Francisco García-Cozar
Hepatitis C virus (HCV) infection is currently the most important cause of chronic viral hepatitis in the world and one of the most frequent indications for liver transplantation. HCV uses different strategies to evade the innate and adaptive immune response, and this evasion plays a key role in determining viral persistence. Several HCV viral proteins have been described as immune modulators. In this review, we will focus on the effect of HCV nucleocapsid core protein in the function of immune cells and its correlation with the findings observed in HCV chronically infected patients...
January 16, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28067225/hepatitis-c-virus-has-a-genetically-determined-lymphotropism-through-co-receptor-b7-2
#20
Chia-Lin Chen, Jeffrey Y Huang, Chun-Hsiang Wang, Stanley M Tahara, Lin Zhou, Yasuteru Kondo, Joel Schechter, Lishan Su, Michael M C Lai, Takaji Wakita, François-Loïc Cosset, Jae U Jung, Keigo Machida
B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells...
January 9, 2017: Nature Communications
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