Immune responses throughout hepatitis C virus (HCV) infection: HCV from the immune system point of view

1997 ◽  
Vol 19 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Sergio Abrignani
Keyword(s):  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Immune Responses ◽  
Point Of View ◽  
Hcv Infection ◽  
System Point

scholarly journals Hepatitis C virus evades IFN signaling by suppressing long non-coding RNA Linc-Pint involving c/EBP-β

2021 ◽  
Author(s):  
Mousumi Khatun ◽  
Jinsong Zhang ◽  
Ranjit Ray ◽  
Ratna B. Ray
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Immune Responses ◽  
Promoter Activity ◽  
Innate Immune ◽  
Hcv Infection ◽  
Positive Regulator

Hepatitis C virus (HCV) regulates many cellular genes in modulating host immune system for benefit of viral replication and long-term persistence in a host for chronic infection. Long non-coding RNAs (lncRNAs) play an important role in the regulation of many important cellular processes, including immune responses. We recently reported that HCV infection downregulates lncRNA Linc-Pint expression, although the mechanism of repression and functional consequence are not well understood. In this study, we demonstrated that HCV infection of hepatocytes transcriptionally reduces Linc-Pint expression through CCAAT/enhancer binding protein-β (C/EBP-β). Subsequently, we observed that overexpression of Linc-Pint significantly upregulates IFN-α and IFN-β expression in HCV replicating hepatocytes. Using unbiased proteomics, we identified Linc-Pint associates with DDX24, which enables RIP1 to interact with IRF7 of IFN signaling pathway. We further observed that IFN-α-14 promoter activity was enhanced in the presence of Linc-Pint. Together, these results demonstrated that Linc-Pint acts as a positive regulator of host innate immune responses, specially IFN signaling. HCV mediated downregulation of Linc-Pint expression appeared as one of the mechanisms by which HCV may evade innate immunity for long-term persistence and chronicity. IMPORTANCE The mechanism by which lncRNA regulates host immune response during HCV infection is poorly understood. We observed that Linc-Pint was transcriptionally downregulated by HCV. Using ChIP assay, we showed inhibition of transcription factor C/EBP-β binding to the Linc-pint promoter in the presence of HCV infection. We further identified that Linc-Pint associates with DDX24 for immune modulatory function. Overexpression of Linc-Pint reduces DDX24 expression which in turn results in disruption of DDX24-RIP1 complex formation and activation of IRF7. An induction of IFN-α14 promoter activity in the presence of Linc-Pint further confirms our observation. Together, our results suggest that Linc-Pint acts as a positive regulator of host innate immune response. Downregulation of Linc-Pint expression by HCV helps in escaping innate immune system for development of chronicity.

A Serological Storm

1970 ◽  
Vol 9 (2) ◽  
Author(s):  
Bertha Wong MD ◽  
Maria Bagovich MD ◽  
Ivan Blasutig PhD ◽  
Simon Carette MD MPhil
Keyword(s):  
Differential Diagnosis ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Clinical Context ◽  
Autoantibody Profile ◽  
Life Threatening ◽  
Clinically Significant ◽  
Sensory Polyneuropathy

This article describes a patient presenting with a sensory polyneuropathy and multiple autoantibodies, leading to the diagnosis of hepatitis C virus (HCV) infection. His widely positive autoantibody profile in the absence of clinically significant rheumatic disease illustrates the importance of interpreting autoimmune serology in the appropriate clinical context and the concept of HCV being a non-specific activator of the immune system. In addition, it highlights the importance of considering untreated HCV infection in the differential diagnosis of rheumatic complaints, particularly if the workup reveals multiple autoantibodies, as HCV is a potentially severe and life-threatening disease, which can be appropriately managed with effective antiviral therapy.

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 Epistatic Effects of Immunoglobulin GM and KM Allotypes on Outcome of Infection with Hepatitis C Virus

2004 ◽  
Vol 78 (9) ◽  
pp. 4561-4565 ◽  
Author(s):  
Janardan P. Pandey ◽  
Jacquie Astemborski ◽  
David L. Thomas
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Hcv Infection ◽  
Fcγ Receptors ◽  
Epistatic Interactions ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Similar Association ◽  
Gm And Km Allotypes

ABSTRACT Immunoglobulin GM and KM allotypes—genetic markers of γ and κ chains, respectively—are associated with immune responsiveness to several infectious pathogens and with survival in certain viral epidemics. We hypothesized that GM and KM allotypes affect the outcome of hepatitis C virus (HCV) infection. To test this hypothesis, we serologically allotyped 100 persons with well-documented clearance of HCV infection and 198 matched persistently infected persons. None of the GM or KM phenotypes by itself was associated with the clearance or persistence of HCV infection. Particular combinations of these phenotypes, however, were significantly associated with the outcome of HCV infection. Subjects with GM 1,17 5,13 and KM 1,3 phenotypes were over three times (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.44 to 8.87) as likely to clear the infection as the subjects who lacked these phenotypes. This GM phenotype had a similar association with clearance in the absence of KM 3 (OR, 2.75; 95% CI, 1.21 to 6.23). The presence of GM 1,3,17 23 5,13 phenotype (in the absence of KM 3) was associated with persistence (OR, 0.21; 95% CI, 0.06 to 0.77), while its absence (in the presence of KM 1,3) was associated with the clearance of infection (OR, 2.03; 95% CI, 1.16 to 3.54). These results show epistatic interactions of genes on chromosomes 14 (GM) and 2 (KM) in influencing the outcome of an HCV infection. Further investigations involving candidate genes (GM, KM, HLA, and Fcγ receptors) and cellular and humoral immune responses to HCV epitopes are needed to understand the mechanisms underlying these associations.

scholarly journals In Vivo Study of the HC-TN Strain of Hepatitis C Virus Recovered from a Patient with Fulminant Hepatitis: RNA Transcripts of a Molecular Clone (pHC-TN) Are Infectious in Chimpanzees but Not in Huh7.5 Cells

2007 ◽  
Vol 81 (13) ◽  
pp. 7208-7219 ◽  
Author(s):  
Akito Sakai ◽  
Shingo Takikawa ◽  
Robert Thimme ◽  
Jean-Christophe Meunier ◽  
Hans Christian Spangenberg ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Viral Evolution ◽  
Acute Infection ◽  
Hcv Infection ◽  
Rna Transcripts

ABSTRACT Both viral and host factors are thought to influence the pathogenesis of hepatitis C virus (HCV) infection. We studied strain HC-TN (genotype 1a), which caused fulminant hepatic failure in a patient and, subsequently, severe hepatitis in a chimpanzee (CH1422), to analyze the relationship between disease severity, host immune response, viral evolution, and outcome. A second chimpanzee (CH1581) was infected from CH1422 plasma, and a third chimpanzee (CH1579) was infected from RNA transcripts of a consensus cDNA of HC-TN (pHC-TN). RNA transcripts of pHC-TN did not replicate in Huh7.5 cells, which were recently found to be susceptible to infection with another fulminant HCV strain (JFH1). The courses of viremia were similar in the three animals. However, CH1581 and CH1579 developed a less severe acute hepatitis than CH1422. CH1579 and CH1422 resolved the infection, whereas CH1581 became persistently infected. CH1579 and CH1581, despite their differing outcomes, both developed significant intrahepatic cellular immune responses, but not antibodies to the envelope glycoproteins or neutralizing antibodies, during the acute infection. We analyzed the polyprotein sequences of virus recovered at five and nine time points from CH1579 and CH1581, respectively, during the first year of follow-up. High mutation rates and high proportions of nonsynonymous mutations suggested immune pressure and positive selection in both animals. Changes were not selected until after the initial decrease in virus titers and after the development of immune responses and hepatitis. Subsequently, however, mutations emerged repeatedly in both animals. Overall, our results indicate that disease severity and outcome of acute HCV infection depend primarily on the host response.

scholarly journals Detection of host immune responses in acute phase sera of spontaneous resolution versus persistent hepatitis C virus infection

2012 ◽  
Vol 93 (8) ◽  
pp. 1673-1679 ◽  
Author(s):  
Suganya Selvarajah ◽  
Sheila Keating ◽  
John Heitman ◽  
Kai Lu ◽  
Graham Simmons ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Serum Levels ◽  
Hcv Infection ◽  
Serum Samples ◽  
Necrosis Factor Alpha ◽  
Acute Hcv ◽  
Chronic Hcv ◽  
Acute Hcv Infection

Prior to the identification of hepatitis C virus (HCV), transfusion-transmission was common. Viral transmission in subjects with a known date of infection allows the study of the immune responses to acute HCV infection. We analysed 39 soluble immune factors in serum samples from subjects with transfusion-transmitted HCV. Dynamic expression kinetics of interferon gamma-induced protein 10 (IP-10), tumour necrosis factor-alpha and interleukin (IL)-10 were observed during acute HCV infection. Serum IP-10 was the only analyte that was significantly elevated in HCV resolvers compared with uninfected controls. In individuals who progressed to chronic HCV elevated levels of IP-10 and IL-10 coincided with first significant alanine aminotransferase elevation and remained elevated during the first year of acute HCV infection. In addition to monitoring lack of reduction in viral load, serum levels of IP-10 and IL-10 expression during acute HCV infection may be useful biomarkers to predict the progress to chronic HCV.

scholarly journals Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia

Gut ◽  
1999 ◽  
Vol 44 (3) ◽  
pp. 424-429 ◽  
Author(s):  
M E Cramp ◽  
P Carucci ◽  
S Rossol ◽  
S Chokshi ◽  
G Maertens ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Lymphocyte Activation ◽  
Interferon Γ ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Chronic Hcv ◽  
Lymphocyte Responses

BACKGROUND/AIMSMost patients infected with hepatitis C virus (HCV) develop chronic infection and persistent viraemia. The immune mechanisms responsible for resolution of viraemia remain poorly understood. HCV specific humoral and cellular immune responses in patients with and without viraemia were investigated.METHODSIn vitro T helper (TH) lymphocyte responses to structural and non-structural HCV proteins were determined by means of proliferative response and cytokine production in 35 anti-HCV positive/HCV RNA negative patients and in 31 patients with chronic HCV infection and persistent viraemia. Humoral responses were determined by measuring HCV specific antibody quantity and specificity.RESULTSA TH response to two or more HCV proteins was present in 18 of 35 patients with serological viral clearance compared with just one of 31 viraemic patients (p = 0.00001). HCV specific interferon-γ production was increased only in the former group. In contrast, the antibody levels were significantly lower and directed at fewer HCV antigens in patients with undetectable HCV RNA.CONCLUSIONSPatients without viraemia after HCV infection frequently have strong TH lymphocyte responses of the TH1 type to multiple HCV antigens many years after the onset of infection, whereas antibody responses are less marked. These results suggest that control of HCV replication may depend on effective TH lymphocyte activation.

scholarly journals Immune Response of Cytotoxic T Lymphocytes and Possibility of Vaccine Development for Hepatitis C Virus Infection

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Kazumasa Hiroishi ◽  
Junichi Eguchi ◽  
Shigeaki Ishii ◽  
Ayako Hiraide ◽  
Masashi Sakaki ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Cytotoxic T Lymphocytes ◽  
Vaccine Development ◽  
Hcv Infection ◽  
Ctl Response ◽  
Host Immune Responses ◽  
Ctl Responses

Immune responses of cytotoxic T lymphocytes (CTLs) are implicated in viral eradication and the pathogenesis of hepatitis C. Weak CTL response against hepatitis C virus (HCV) may lead to a persistent infection. HCV infection impairs the function of HCV-specific CTLs; HCV proteins are thought to actively suppress host immune responses, including CTLs. Induction of a strong HCV-specific CTL response in HCV-infected patients can facilitate complete HCV clearance. Thus, the development of a vaccine that can induce potent CTL response against HCV is strongly expected. We investigated HCV-specific CTL responses by enzyme-linked immuno-spot assay and/or synthetic peptides and identified over 40 novel CTL epitopes in the HCV protein. Our findings may contribute to the development of the HCV vaccine. In this paper, we describe the CTL responses in HCV infection and the attempts at vaccine development based on recent scientific articles.

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