scholarly journals Hepatitis C Virus Evasion from RIG-I-Dependent Hepatic Innate Immunity

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Helene Minyi Liu ◽  
Michael Gale
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Intracellular Signaling ◽  
Innate Immune ◽  
Hcv Infection ◽  
Viral Pathogen ◽  
Infected Hepatocyte ◽  
Interferon Stimulated Genes ◽  
Hepatic Innate Immunity ◽  
Chronic Hcv

Exposure to hepatitis C virus (HCV) usually results in persistent infection that often develops into chronic liver disease. Interferon-alpha (IFN) treatment comprises the foundation of current approved therapy for chronic HCV infection but is limited in overall efficacy. IFN is a major effector of innate antiviral immunity and is naturally produced in response to viral infection when viral pathogen-associated molecular patterns (PAMPs) are recognized as nonself and are bound by cellular pathogen recognition receptors (PRRs), including Toll-like receptors (TLRs) and the RIG-I-like receptors (RLRs). Within hepatocytes, RIG-I is a major PRR of HCV infection wherein PAMP interactions serve to trigger intracellular signaling cascades in the infected hepatocyte to drive IFN production and the expression of interferon-stimulated genes (ISGs). ISGs function to limit virus replication, modulate the immune system, and to suppress virus spread. However, studies of HCV-host interactions have revealed several mechanisms of innate immune regulation and evasion that feature virus control of PRR signaling and regulation of hepatic innate immune programs that may provide a molecular basis for viral persistence.

scholarly journals Differential expression of viral pathogen-associated molecular pattern receptors mRNA in Egyptian chronic hepatitis C virus patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Reda A. Suef ◽  
Ezz Elden M. Mohamed ◽  
Mohamed T. M. Mansour ◽  
Kilian Weigand ◽  
Mohamed M. S. Farag
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Surveillance ◽  
Innate Immune ◽  
Control Group ◽  
Mrna Levels ◽  
Viral Pathogen ◽  
Expression Levels ◽  
Subsequent Decrease ◽  
Chronic Hcv

Abstract Background One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-α to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-α in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls. Results The expression levels of TLR3, TLR7, and IFN-α were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-α) compared to control group. Obviously, the expression levels of IFN-α were positively correlated with the levels of both TLR3 and TLR7. Conclusion The exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-α production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies.

scholarly journals Editorial. The Role of Autophagy in Hepatitis C Virus Infection

2012 ◽  
Vol 1 (1) ◽  
pp. 1-6
Author(s):  
Jun Cheng ◽  
Min Quan ◽  
Liang Wu ◽  
Qi Wang
Keyword(s):  
Life Cycle ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Infected Hepatocyte ◽  
Unfolded Protein ◽  
Autophagy Induction ◽  
New Strategy ◽  
Chronic Hcv ◽  
Protein Response

Abstract Hepatitis C virus (HCV) infects ≈2% of the world’s population. HCV infection not only causes acute and chronic hepatitis, but also leads to liver cirrhosis and hepatocellular carcinoma (HCC). The molecular pathogenesis of HCV infection has been explored and many evidence indicated that autophagy is an important process for its life cycle, although autophagy was thought as a mechanism to eliminate invaded HCV from hepatocyte. Structural and non-structural proteins of HCV are important regulators of autophagy, and HCV uses autophagy as a necessary step in its replication. Down-regulation of innate immune response by HCV through unfolded protein response (UPR) and autophagy induction was used as a pathway to establish chronic HCV infection in the liver. Meanwhile, the infected hepatocyte is also using autophagy mechanism to eradicate HCV virus from liver. The study on relationship between HCV and autophagy will pave the new way to understand HCV life cycle and to find new strategy for prevention and treatment of liver diseases caused by HCV infection.

Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

2011 ◽  
Vol 152 (22) ◽  
pp. 876-881
Author(s):  
Alajos Pár
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Polymorphisms ◽  
Chronic Hepatitis C ◽  
Genome Wide Association Study ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Snp Analysis ◽  
Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

scholarly journals Hepatitis C Virus Induces Toll-Like Receptor 4 Expression, Leading to Enhanced Production of Beta Interferon and Interleukin-6

2006 ◽  
Vol 80 (2) ◽  
pp. 866-874 ◽  
Author(s):  
Keigo Machida ◽  
Kevin T. H. Cheng ◽  
Vicky M.-H. Sung ◽  
Alexandra M. Levine ◽  
Steven Foung ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cells ◽  
Immune Responses ◽  
Interleukin 6 ◽  
Innate Immune ◽  
Hcv Infection ◽  
Innate Immune Responses ◽  
Altered Expression ◽  
Beta Interferon

ABSTRACT Hepatitis C virus (HCV) induces inflammatory signals, leading to hepatitis, hepatocellular carcinomas, and lymphomas. The mechanism of HCV involvement in the host's innate immune responses has not been well characterized. In this study, we analyzed expression and regulation of the entire panel of toll-like receptors (TLRs) in human B cells following HCV infection in vitro. Among all of the TLRs (TLRs 1 to 10) examined, only TLR4 showed an altered expression (a three- to sevenfold up-regulation) after HCV infection. Peripheral blood mononuclear cells from HCV-infected individuals also showed a higher expression level of TLR4 compared with those of healthy individuals. HCV infection significantly increased beta interferon (IFN-β) and interleukin-6 (IL-6) secretion from B cells, particularly after lipopolysaccharide stimulation. The increased IFN-β and IL-6 production was mediated by TLR4 induction, since the introduction of the small interfering RNA against TLR4 specifically inhibited the HCV-induced cytokine production. Among all of the viral proteins, only NS5A caused TLR4 induction in hepatocytes and B cells. NS5A specifically activated the promoter of the TLR4 gene in both hepatocytes and B cells. In conclusion, HCV infection directly induces TLR4 expression and thereby activates B cells, which may contribute to the host's innate immune responses.

scholarly journals Proteasome Activator PA28γ-Dependent Nuclear Retention and Degradation of Hepatitis C Virus Core Protein

2003 ◽  
Vol 77 (19) ◽  
pp. 10237-10249 ◽  
Author(s):  
Kohji Moriishi ◽  
Tamaki Okabayashi ◽  
Kousuke Nakai ◽  
Kyoji Moriya ◽  
Kazuhiko Koike ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Regulatory Protein ◽  
Hcv Infection ◽  
Nuclear Retention ◽  
Proteasome Activator ◽  
Hcv Core Protein ◽  
Core Proteins ◽  
Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) core protein plays an important role in the formation of the viral nucleocapsid and a regulatory protein involved in hepatocarcinogenesis. In this study, we have identified proteasome activator PA28γ (11S regulator γ) as an HCV core binding protein by using yeast two-hybrid system. This interaction was demonstrated not only in cell culture but also in the livers of HCV core transgenic mice. These findings are extended to human HCV infection by the observation of this interaction in liver specimens from a patient with chronic HCV infection. Neither the interaction of HCV core protein with other PA28 subtypes nor that of PA28γ with other Flavivirus core proteins was detected. Deletion of the PA28γ-binding region from the HCV core protein or knockout of the PA28γ gene led to the export of the HCV core protein from the nucleus to the cytoplasm. Overexpression of PA28γ enhanced the proteolysis of the HCV core protein. Thus, the nuclear retention and stability of the HCV core protein is regulated via a PA28γ-dependent pathway through which HCV pathogenesis may be exerted.

Direct-acting Antivirals for Hepatitis C Virus in Patients on Maintenance Dialysis

2017 ◽  
Vol 40 (10) ◽  
pp. 531-541 ◽  
Author(s):  
Fabrizio Fabrizi ◽  
Francesca M. Donato ◽  
Piergiorgio Messa
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Severe Renal Impairment ◽  
Controlled Trial ◽  
Hcv Infection ◽  
Direct Acting Antivirals ◽  
Safety And Efficacy ◽  
Maintenance Dialysis ◽  
Chronic Hcv ◽  
Direct Acting

The frequency of hepatitis C virus (HCV) infection remains high in patients with chronic kidney disease (CKD) and plays a detrimental role in mortality in this population. According to the latest survey, the adjusted hazard ratio for HCV-positive versus HCV-negative patients on long-term dialysis was 1.12 (95% CI, 1.05 to 1.20) and 1.10 (95% CI, 0.98 to 1.22) for all-cause and cardiovascular mortality, respectively. An impairment on quality of life has also been documented in HCV-infected patients undergoing regular dialysis. Most clinicians have been so far reluctant to treat hepatitis C in patients with advanced CKD, due to concerns regarding low efficacy and safety of interferon-based regimens. The advent of all-oral, direct-acting antivirals (DAAs) has revolutionized treatment paradigms for HCV, including patients with other comorbidities such as CKD. Two combinations of DAAs have been recently approved for the treatment of HCV in advanced CKD: elbasvir/grazoprevir (evaluated in 1 randomized controlled trial) and ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin (examined in some observational, single-arm studies). These antiviral combinations have provided high safety and efficacy (SVR12 rates >90%) in HCV-infected patients with stage 4–5 CKD. Sofosbuvir, a nucleotide analogue inhibitor of the HCV NS5B polymerase, is the cornerstone of most anti-HCV current regimens but is not currently recommended for patients with severe renal insufficiency (eGFR <30 mL/min per 1.73 m2). However, several small-sized studies have been published on the safety and efficacy of sofosbuvir-based regimens for patients with hepatitis C on maintenance dialysis>; overall, the viral response was satisfactory (SVR12 rates ranging between 58% and 100%) with a few drug-related drop-outs. Studies are in progress to assess whether ribavirin-free antiviral combinations with novel DAAs are a viable option for patients with severe renal impairment and chronic HCV infection.

IgM and IgA antibodies generated against hepatitis C virus core antigen in patients with acute and chronic HCV infection

1994 ◽  
Vol 39 (9) ◽  
pp. 2022-2031 ◽  
Author(s):  
Shinjiro Sato ◽  
Shigetoshi Fujiyama ◽  
Motohiko Tanaka ◽  
Masafumi Goto ◽  
Yuko Taura ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Core Antigen ◽  
Virus Core ◽  
Iga Antibodies ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

scholarly journals Sustained Virological Response after 8-Week Treatment of Simeprevir with Peginterferon α-2a plus Ribavirin in a Japanese Female with Hepatitis C Virus Genotype 1b and IL28B Minor Genotype

2015 ◽  
Vol 9 (2) ◽  
pp. 215-220 ◽  
Author(s):  
Tatsuo Kanda ◽  
Masato Nakamura ◽  
Reina Sasaki ◽  
Shin Yasui ◽  
Shingo Nakamoto ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Events ◽  
Sustained Virological Response ◽  
Virological Response ◽  
Hcv Infection ◽  
Direct Acting Antivirals ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Peginterferon Α

Direct-acting antivirals with or without peginterferon α (PEG-IFN α) plus ribavirin are now available for the treatment of hepatitis C virus (HCV) infection. Direct-acting antivirals are potent inhibitors of HCV replication, but some of them occasionally possess serious adverse events. We experienced a 64-year-old female with chronic HCV genotype 1b infection who showed elevated alanine aminotransferase of 528 IU/l at week 9 after the commencement of treatment of simeprevir with PEG-IFN α-2a plus ribavirin. However, she achieved sustained virological response at week 24 after the end of treatment. In Japan, we also have to treat elderly patients infected with HCV and/or advanced hepatic fibrosis. Until an effective interferon-free regimen is established, direct-acting antivirals with PEG-IFN plus ribavirin may still play a role in the treatment for certain patients. To avoid serious results from adverse events, careful attention and follow-up will be needed in the treatment course of simeprevir with PEG-IFN plus ribavirin for chronic HCV infection.

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