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Immune response to HCV

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https://www.readbyqxmd.com/read/28067225/hepatitis-c-virus-has-a-genetically-determined-lymphotropism-through-co-receptor-b7-2
#1
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
https://www.readbyqxmd.com/read/28045877/the-path-to-cancer-and-back-immune-modulation-during-hepatitis-c-virus-infection-progression-to-fibrosis-and-cancer-and-unexpected-roles-of-new-antivirals
#2
Jose D Debes, Robert J de Knegt, Andre Boonstra
Hepatitis C virus (HCV) infection affects over 130 million individuals worldwide, and it is the number 1 reason for liver transplantation in the United States. HCV infection progresses in a slow chronic fashion eliciting a strong but ineffective immune response, mainly characterized by NK cell dysfunction and T cell exhaustion. The chronic hepatic inflammation leads to liver fibrosis, cirrhosis and cancer in a significant number of patients. In recent years, groundbreaking research has led to the discovery of new HCV-specific direct acting antivirals (DAAs), which have an unprecedented efficacy to clear the virus, and establish a sustained virological response...
December 30, 2016: Transplantation
https://www.readbyqxmd.com/read/28040549/increased-peripheral-cd4-regulatory-t-cells-persist-after-successful-direct-acting-antiviral-treatment-of-chronic-hepatitis-c
#3
Bettina Langhans, Hans Dieter Nischalke, Benjamin Krämer, Annekristin Hausen, Leona Dold, Peer van Heteren, Robert Hüneburg, Jacob Nattermann, Christian P Strassburg, Ulrich Spengler
INTRODUCTION: CD4(+) regulatory T cells (Tregs) expand during chronic hepatitis C virus (HCV) infection, inhibit antiviral immunity and promote fibrosis. Directly acting antivirals (DAA) have revolutionized HCV therapy. However, it is unclear if Tregs are normalized after DAA-induced HCV elimination. METHODS: We analyzed Tregs before (=baseline), at end of therapy (EOT), 12 and 24 weeks (SVR12, SVR24) and long-term (51±14 weeks) after EOT in 26 genotype-1-infected patients successfully treated with sofosbuvir (SOF) plus IFN/ribavirin (n=12) and IFN-free DAA regimens (SOF plus daclatasvir or simeprevir; n=14)...
December 28, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28036111/hepatic-ifnl4-expression-is-associated-with-non-response-to-interferon-based-therapy-through-the-regulation-of-basal-interferon-stimulated-gene-expression-in-chronic-hepatitis-c-patients
#4
Miyako Murakawa, Yasuhiro Asahina, Fukiko Kawai-Kitahata, Mina Nakagawa, Sayuri Nitta, Satoshi Otani, Hiroko Nagata, Shun Kaneko, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Yasuhito Tanaka, Sayuki Iijima, Kaoru Tsuchiya, Namiki Izumi, Shuju Tohda, Mamoru Watanabe
Single nucleotide polymorphisms (SNPs) within or near interferon lambda 4 (IFNL4) gene located upstream of IFNL3 are associated with response to anti-HCV therapy both in interferon (IFN)-based and IFN-free regimens. IFNL4 encodes IFNλ4, a newly discovered type III IFN, and its expression is controlled by rs368234815-TT/ΔG, which is in strong linkage disequilibrium (LD) with other tag SNPs within or near IFNL4 such as rs12979860 and rs8099917. Intrahepatic expression levels of IFN-stimulated genes (ISGs) affect the responsiveness to IFNα and are also associated with IFNL4 genotype...
December 30, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/28035208/regulatory-t-cells-in-hepatitis-b-and-c-virus-infections
#5
REVIEW
Min Kyung Jung, Eui-Cheol Shin
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotropic viruses that establish chronic persistent infection by effectively escaping the host immune response and can cause immune-mediated liver injury. It has recently become apparent that regulatory T (Treg) cells, specifically CD4(+)CD25(+)Foxp3(+) Treg cells, modulate viral diseases by suppressing antiviral immune responses and regulating inflammatory host injury. The roles of Treg cells in HBV and HCV infections range from suppressing antiviral T cell responses to protecting the liver from immune-mediated damage...
December 2016: Immune Network
https://www.readbyqxmd.com/read/27997681/the-core-domain-of-hepatitis-c-virus-glycoprotein-e2-generates-potent-cross-neutralizing-antibodies
#6
Patricia Vietheer, Irene Boo, Jun Gu, Kathleen McCaffrey, Stirling Edwards, Catherine Owczarek, Matthew P Hardy, Louis Fabri, Rob J Center, Pantelis Poumbourios, Heidi E Drummer
: A vaccine that prevents hepatitis C virus (HCV) infection is urgently needed to support an emerging global elimination program. However, vaccine development has been confounded because of HCV's high degree of antigenic variability and the preferential induction of type-specific immune responses with limited potency against heterologous viral strains and genotypes. We showed previously that deletion of the three variable regions from the E2 receptor-binding domain (Δ123) increases the ability of human broadly neutralizing antibodies (bNAbs) to inhibit E2-CD81 receptor interactions, suggesting improved bNAb epitope exposure...
December 20, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27984060/identification-of-drug-resistance-and-immune-driven-variations-in-hepatitis-c-virus-hcv-ns3-4a-ns5a-and-ns5b-regions-reveals-a-new-approach-toward-personalized-medicine
#7
Aqsa Ikram, Ayesha Obaid, Faryal Mehwish Awan, Rumeza Hanif, Anam Naz, Rehan Zafar Paracha, Amjad Ali, Hussnain Ahmed Janjua
Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection...
January 2017: Antiviral Research
https://www.readbyqxmd.com/read/27983476/tnf-superfamily-members-promote-hepatitis-c-virus-entry-via-an-nf-%C3%AE%C2%BAb-and-myosin-light-chain-kinase-dependent-pathway
#8
Nicola Fletcher, Andrew R Clark, Peter Balfe, Jane McKeating
Preventing viral induced liver disease begins with an understanding of the host factors that define susceptibility to infection. Hepatitis C Virus (HCV) is a global health issue with an estimated 170 million infected individuals at risk of developing liver disease including fibrosis and hepatocellular carcinoma. The liver is the major reservoir supporting HCV replication and this hepatocellular tropism is defined by HCV engagement of cellular entry receptors. Hepatocytes are polarised in vivo and this barrier function limits HCV entry...
December 15, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27941432/immune-reconstitution-following-hcv-clearance-with-direct-antiviral-agents-potential-consequences-for-patients-with-hcc
#9
Jens M Werner, Akinbami Adenugba, Ulrike Protzer
Recent introduction of all-oral direct acting antiviral treatment has revolutionized care of patients with chronic hepatitis C virus infection. Since patients with different liver disease stages have been treated with great success including those awaiting liver transplantation, therapy has been extended to patients with hepatocellular carcinoma as well. From observational studies among compensated cirrhotic hepatitis C patients treated with interferon-containing regimens, it would have been expected that the rate of hepatocellular carcinoma occurrence is markedly decreased after a sustained virological response...
December 8, 2016: Transplantation
https://www.readbyqxmd.com/read/27934839/internalisation-of-hepatitis-c-virus-core-protein-by-human-conjunctival-fibroblasts
#10
A R Rajalakshmy, J Malathi, H N Madhavan, S Bhaskar, G K Iyer
Recent studies indicate that hepatitis C virus (HCV) proteins can mediate innate immune response and inflammation in conjunctival fibroblasts which contributes to the pathology of dry eye condition associated with chronic HCV infection. The present study investigates the phagocytic potential of human conjunctival fibroblasts (HCFj) for HCV core protein. HCFj cells were incubated with HCV core antigen for different periods of time, and fluorescent micrographs were taken to observe protein internalisation. HCFj cells were capable of internalising HCV core antigen within 1 h; this gives an insight into another molecular mechanism which may contribute towards HCV-associated conjunctival inflammation...
October 2016: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27910749/role-of-toll-like-receptors-in-hepatitis-c-virus-pathogenesis-and-treatment
#11
Usman Ali Ashfaq, Muhammad Sarfaraz Iqbal, Saba Khaliq
Viral infections are rising every day, and viruses appear to be the most dangerous pathogens in the world. Hepatitis C virus (HCV) is accepted as one of the major destructive factors of promoting severe hepatic disorders by infecting more than 180 million individuals throughout the world. Chronic infection caused by HCV poses a serious global health emergency and appears to be a powerful threat to humanity. Almost 20 years have passed since the disclosure of HCV, but even now, treatment preferences remain limited...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27902444/oncolytic-reovirus-as-a-combined-antiviral-and-anti-tumour-agent-for-the-treatment-of-liver-cancer
#12
Adel Samson, Matthew J Bentham, Karen Scott, Gerard Nuovo, Abigail Bloy, Elizabeth Appleton, Robert A Adair, Rajiv Dave, Adam Peckham-Cooper, Giles Toogood, Seishi Nagamori, Matthew Coffey, Richard Vile, Kevin Harrington, Peter Selby, Fiona Errington-Mais, Alan Melcher, Stephen Griffin
OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. DESIGN AND RESULTS: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication...
November 15, 2016: Gut
https://www.readbyqxmd.com/read/27902328/hepatitis-c-virus-core-activates-proteasomal-activator-28-gamma-expression-via-upregulation-of-p53-levels-to-control-virus-propagation
#13
Juri Kwak, Indira Tiwari, Kyung Lib Jang
The proteasomal activator PA28γ, frequently overexpressed in hepatocellular carcinoma (HCC), is believed to play several important roles in hepatitis C virus (HCV) replication and viral pathogenesis. However, the underlying mechanism for PA28γ overexpression in HCC and its role during HCV replication are still unclear. In the present study, we found that HCV Core derived from either ectopic expression or HCV infection upregulates PA28γ levels in p53-positive human hepatocytes. For this effect, HCV Core sequentially activated ataxia telangiectasia mutated and checkpoint kinase 2 via phosphorylation at Ser-1981 and Thr-68 residues, respectively, resulting in stabilization of p53 via phosphorylation at Ser-15 and Ser-20 residues and subsequent transcriptional activation of PA28γ expression...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902325/targeting-naturally-occurring-epitope-variants-of-hepatitis-c-virus-with-high-affinity-t-cell-receptors
#14
Huajun Zhang, Jianbing Zhang, Lei Chen, Zhiming Weng, Ye Tian, Haifeng Zhao, Youjia Li, Lin Chen, Zhaoduan Liang, Hongjun Zheng, Wenzhuo Zhao, Shi Zhong, Yi Li
Hepatitis C virus (HCV) readily establishes chronic infection, which is characterized by failure of virus-specific CD8+ T cells. HCV uses epitope mutation and T-cell exhaustion to escape from the host immune response. Previously, we engineered high-affinity T-cell receptors (HATs) targeting HIV escape mutants. In this study, the affinity of a T-cell receptor specific for the human leukocyte antigen (HLA)-A2-restricted HCV immunodominant epitope NS3 1406-1415 (KLVALGINAV) was improved from a KD of 6.6 µM to 40 pM...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27888401/the-impact-of-chronic-hepatitis-c-infection-on-cholesterol-metabolism-in-pbmcs-is-associated-with-microrna-146a-expression
#15
M Sidorkiewicz, M Grek, B Jozwiak, A Krol, A Piekarska
Chronic hepatitis C (CHC) infection is known to induce important changes in host cholesterol metabolism. MicroRNAs (miRNAs) regulate the expression of many genes and, in consequence, control various processes, including human metabolism and response to viral infection. Recently, the alteration of the immune-associated miR-146a, which is abundantly present in peripheral blood mononuclear cells (PBMCs), was found in some viral infections. The study aimed to analyse the influence of hepatitis C virus (HCV) infection on miR-146a expression in PBMCs in vivo and in vitro, as well as to assess the possible impact of miR-146a alteration on the intracellular cholesterol level in PBMCs...
November 25, 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27888126/understanding-the-complex-evolution-of-rapidly-mutating-viruses-with-deep-sequencing-beyond-the-analysis-of-viral-diversity
#16
REVIEW
Preston Leung, Auda A Eltahla, Andrew R Lloyd, Rowena A Bull, Fabio Luciani
With the advent of affordable deep sequencing technologies, detection of low frequency variants within genetically diverse viral populations can now be achieved with unprecedented depth and efficiency. The high-resolution data provided by next generation sequencing technologies is currently recognised as the gold standard in estimation of viral diversity. In the analysis of rapidly mutating viruses, longitudinal deep sequencing datasets from viral genomes during individual infection episodes, as well as at the epidemiological level during outbreaks, now allow for more sophisticated analyses such as statistical estimates of the impact of complex mutation patterns on the evolution of the viral populations both within and between hosts...
November 22, 2016: Virus Research
https://www.readbyqxmd.com/read/27888038/evidence-of-bottleneck-effect-on-hepatitis-c-virus-transmission-between-a-couple-under-interferon-based-therapy
#17
Rafael Alves da Silva, Isabel Maria Vicente Guedes de Carvalho, Renata Prandini Adum de Matos, Lilian Hiromi Tomonari Yamasaki, Cíntia Bittar, Paula Rahal, Ana Carolina Gomes Jardim
Issues on the correlation of viral genetic diversity and treatment response to the hepatitis C infection remain uncertain. The bottleneck effect dictates the characteristics of the viral population that will establish the infection in a new host and is related to how the immune system and treatment will be effective against the virus. Here we evaluated the phylogenetic characteristics of quasispecies population and the treatment response pattern of a HCV infected couple. We also analyzed whether the viral population of these patients indicated that they were exposed to the same source for primer infection...
January 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27885757/role-of-primary-t-cell-immunodeficiency-and-hepatitis-b-coinfection-on-spontaneous-clearance-of-hepatitis-c-the-bc-hepatitis-testers-cohort
#18
N Islam, M Krajden, M Gilbert, P Gustafson, A Yu, M Kuo, M Chong, M Alvarez, J Wong, M W Tyndall, N Z Janjua
T-cell host immune response against hepatitis C virus (HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T-cell deficiency along with other factors on the spontaneous clearance of HCV in a large population-based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked with data on their medical visits, hospitalizations and prescription drugs...
November 25, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27875997/identification-of-the-transcripts-associated-with-spontaneous-hcv-clearance-in-individuals-co-infected-with-hiv-and-hcv
#19
Yue Chen, Chengli Shen, Debjani Guha, Ming Ding, Scott Kulich, Aiymkul Ashimkhanova, Charles Rinaldo, Eric Seaberg, Joseph B Margolick, Valentina Stosor, Otoniel Martínez-Maza, Phalguni Gupta
BACKGROUND: Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20-46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance...
November 22, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27872681/alcohol-use-disorder-and-its-impact-on-chronic-hepatitis-c-virus-and-human-immunodeficiency-virus-infections
#20
REVIEW
Daniel Fuster, Arantza Sanvisens, Ferran Bolao, Inmaculada Rivas, Jordi Tor, Robert Muga
Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease...
November 8, 2016: World Journal of Hepatology
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