scholarly journals Cross-Genotype Immunity to Hepatitis C Virus

2004 ◽  
Vol 78 (3) ◽  
pp. 1575-1581 ◽  
Author(s):  
Robert E. Lanford ◽  
Bernadette Guerra ◽  
Deborah Chavez ◽  
Catherine Bigger ◽  
Kathleen M. Brasky ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Primary Infection ◽  
Vaccine Development ◽  
Amino Acid Level ◽  
Gamma Interferon ◽  
Hcv Infection ◽  
Interferon Response ◽  
Genotype 4 ◽  
Interferon Stimulated Genes

ABSTRACT Recent studies in humans and chimpanzees suggest that immunity can be induced to diminish the incidence of chronic hepatitis C virus (HCV) infection. However, the immunity that promotes viral recovery is poorly understood, and whether the breadth of this adaptive immunity is sufficient to overcome the substantial intergenotype antigenic diversity represents a final obstacle to demonstrating the feasibility of vaccine development. Here we demonstrate that recovery from a genotype 1 HCV infection protects chimpanzees against infection with representatives of other genotypes that exhibit up to 30% divergence at the amino acid level, including challenges with genotype 4, a mixture of genotypes 2 and 3, and a complex inoculum containing genotypes 1, 2, 3, and 4. In each instance, the level and duration of viremia were markedly reduced in comparison to the primary infection in the same animal. The data indicate that epitopes conserved between genotypes must play an essential role in immunity. The inocula used in the rechallenge studies induced typical primary infection profiles in naïve chimpanzees. Rechallenge infections were associated with rapid increases in the intrahepatic transcripts of interferon-stimulated genes, even in animals exhibiting apparent sterilizing immunity. Protective immunity was often associated with an early increase in gamma interferon transcripts in the liver and increases in intrahepatic transcripts of Mig, a T-cell chemokine that is a gamma interferon response gene. These studies are the first to show that cross-genotype immunity can be induced to HCV, demonstrating the feasibility of developing a vaccine protective against all HCV strains.

scholarly journals PREVALENCE AND GENOTYPING OF HEPATITIS C VIRUS IN HEMODIALYSIS PATIENTS AND EVALUATION OF HCV-CORE ANTIGEN TEST IN SCREENING PATIENTS FOR DIALYSIS IN SANA'A CITY, YEMEN

2019 ◽  
Author(s):  
Samira H Hanash ◽  
Hassan A. Al-Shamahy ◽  
Mohammed Hussein Saleh Bamshmous
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
General Population ◽  
Predictive Power ◽  
Hcv Infection ◽  
Health Concern ◽  
Core Antigen ◽  
Antigen Test ◽  
Genotype 4 ◽  
Hcv Core Antigen

Hepatitis C virus infection is a constant worldwide public health concern. The prevalence of HCV infection is higher in patients on chronic haemodialysis (HD) than in the general population. Despite the control of blood products, hepatitis C virus transmission is still being observed among patients undergoing dialysis. Detection systems for serum HCV antibodies are insensitive in the acute phase because of the long serological window. Direct detection of HCV depends on PCR test but this test is not suitable for routine screening. The objective of this study was to determine prevalence of HCV, genotyping and if HCV core antigen test could be a better alternative to NAT techniques for the diagnosis of HCV infection during the window period and whether the sensitivity for antibody detection is preserved. We screened 159 patients on long-term dialysis by HVC antibodies test, PCR HCV-RNA and HCV core antigen test by commercial tests. The prevalence of HCV was 10.7% (17 patients) and genotype 4 was the most common one (64.7%). The sensitivity of HCV core antigen test was 94.1%, the specificity 100%, the positive predictive power 100%, and the negative predictive power 97.9%. In conclusions; patients on maintenance HD in Yemen have a high prevalence of HCV infection comparing with general population; and genotype 4 is predominant. The performance of serological detection of HCV core antigen was better than that of HCV antibodies test and may be an alternative to nucleic acid amplification technology (NAT) for routine monitoring of patients on chronic dialysis.

scholarly journals Chronic hepatitis C virus infection: Is there a correlation between HCV genotypes and the level of viremia?

2006 ◽  
Vol 59 (5-6) ◽  
pp. 230-234 ◽  
Author(s):  
Dragan Delic ◽  
Zorica Nesic ◽  
Jasmina Simonovic ◽  
Neda Svirtlih ◽  
Ljubisa Dokic ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Objective Assessment ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Genotype 4 ◽  
Hcv Genotypes ◽  
Genotype 2 ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Introduction. Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. Material and methods. For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested. Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype lb infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. Results. Patients infected by genotype lb had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p<0.05). Over 70% of patients infected by genotype lb had more than 2xl06 virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7x10.6 virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3xl06 copies/ml; p<0.05). Conclusion. Our results are in concordance with the results of other authors reporting that genotype lb is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype lb infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems. .

scholarly journals Hepatitis C virus infection of primary tupaia hepatocytes leads to selection of quasispecies variants, induction of interferon-stimulated genes and NF-κB nuclear translocation

2005 ◽  
Vol 86 (11) ◽  
pp. 3065-3074 ◽  
Author(s):  
Anunciata Guitart ◽  
José-Ignacio Riezu-Boj ◽  
Edurne Elizalde ◽  
Esther Larrea ◽  
Carmen Berasain ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Semliki Forest Virus ◽  
Nuclear Translocation ◽  
Natural Infection ◽  
Hcv Infection ◽  
Interferon Response ◽  
Cell Phenotype

Systems for in vitro culture of Hepatitis C virus (HCV) are essential tools to analyse virus–cell interactions and to investigate relevant pathophysiological aspects of HCV infection. Although the HCV replicon methodology has increased our understanding of HCV biology, this system does not reproduce the natural infection. Recently, tupaia (Tupaia belangeri chinensis) hepatocytes have been utilized for in vitro culture of HCV. In the present work, primary tupaia hepatocytes infected in vitro with HCV were used to analyse the evolution of HCV quasispecies in infected cells and the ability of the virus to influence antiviral and proinflammatory responses in cells sustaining virus replication. The results confirmed the potential of tupaia hepatocytes as a model for HCV infection, although this system is limited by rapid loss of differentiated cell phenotype in culture. These findings revealed an extraordinary plasticity of HCV quasispecies, which underwent rapid evolution to tupaia-tropic variants as early as 24 h after infection. It was also shown that HCV could activate interferon-sensitive genes, albeit modestly in comparison with other viruses such as Semliki Forest virus. Importantly, HCV activated NF-κB in primary hepatocytes and upregulated NF-κB-responsive genes including the chemokines MCP-1 and CXCL2 (MIP-2). This effect may play a role in induction of the hepatic inflammatory reaction in vivo. In summary, HCV quasispecies adapt rapidly to the specific biology of the host and HCV stimulates a blunted interferon response while inducing a proinflammatory phenotype in the infected cell.

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 Treatment with Grazoprevir/Elbasvir in Post-kidney Transplant Patients with Hepatitis C Virus Genotype 4 Infection

2021 ◽  
Vol 21 (4) ◽  
Author(s):  
Faisal Abaalkhail ◽  
Waleed Al-hamoudi ◽  
Ibrahim Altraif ◽  
Hazem Mohamed ◽  
Hassan Aleid ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Events ◽  
Kidney Transplant ◽  
Graft Function ◽  
Case Series ◽  
Hcv Infection ◽  
Fixed Dose ◽  
Genotype 4 ◽  
Hcv Genotype

Background: Kidney transplant (KT) recipients have a high rate of hepatitis C virus (HCV) infection, which can impact long-term graft and patient survival rates. Although direct-acting antivirals (DAAs) are effective for treating HCV, there is limited data on their use in post-KT patients with HCV genotype 4 infection. Objectives: To evaluate the effectiveness and occurrence of adverse events with grazoprevir/elbasvir combination treatment without ribavirin in post-KT patients with HCV genotype 4 infection. Methods: In this case series, nine therapy-naïve adult post-KT patients with HCV genotype 4 infection were recruited. They had stable graft function and received a fixed dose of grazoprevir/elbasvir (50 mg/100 mg) combination without ribavirin daily for 12 weeks. Patients co-infected with hepatitis B virus, HIV, or with evidence of decompensated liver disease were excluded from the study. Patients were monitored for viral load, laboratory values, and adverse events associated with drug treatment. The response was defined by the sustained virologic response at 12 weeks (SVR12) after the end of treatment. Results: All nine patients completed the treatment period and achieved SVR12 with no treatment failure or relapse. Of them, six patients had HCV genotype 4 infection alone, and three had HCV of mixed genotypes 1 and 4. Two (22%) patients showed a rapid HCV clearance at four weeks. No adverse events or serious adverse events were reported. The patients’ renal function was stable during and after the treatment with no deterioration of graft function, and no adjustments to the immunosuppressive therapy were required. Conclusions: Grazoprevir/elbasvir combination without ribavirin is an effective and safe treatment option for post-KT patients with genotype 4 HCV infection.

scholarly journals Prevalence and Incidence of Hepatitis C Virus in Hemodialysis Patients in British Columbia: Follow-up after a Possible Breach in Hemodialysis Machines

2009 ◽  
Vol 20 (2) ◽  
pp. e19-e23 ◽  
Author(s):  
Andrew W Tu ◽  
Jane A Buxton ◽  
Mandy Whitlock ◽  
Ognjenka Djurdjev ◽  
Mei Chong ◽  
...  
Keyword(s):  
British Columbia ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Renal Transplant ◽  
South Asia ◽  
Hemodialysis Patients ◽  
Hcv Infection ◽  
Genotype 4 ◽  
Hemodialysis Unit ◽  
Incident Rate

BACKGROUND: A possible breach of the transducer protector in specific dialysis machines was reported in June 2004 in British Columbia (BC), which led to testing of hemodialysis patients for hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV. This testing provided an opportunity to examine HCV incidence, prevalence and coinfection with HBV and HIV, and to compare anti-HCV and HCV polymerase chain reaction (PCR).METHODS: The results of hemodialysis patients who were dialyzed on the implicated machines (65% of BC dialysis patients), and tested for HCV, HBV and HIV, between June 1, 2004, and December 31, 2004, were reviewed and compared with available previous results.RESULTS: Of 1286 hemodialysis patients with anti-HCV and/or HCV-PCR testing, 69 (5.4%) tested positive. Two HCV genotype 4 seroconversions were identified. HCV incidence rate on dialysis was 78.8 cases per 100,000 person-years. Younger age, history of renal transplant and past HBV infection were associated with HCV infection. No occult infection was identified using HCV-PCR.INTERPRETATION: Hemodialysis patients had three times the HCV prevalence rate of the general BC population, and more than 20 times the incident rate of the general Canadian population. One of the two seroconversions occurred before the testing campaign; the patient was likely infected during hemodialysis in South Asia. The other was plausibly a late seroconversion following renal transplant in South Asia. Nosocomial transmission cannot be ruled out because both patients were dialyzed in the same centre. Baseline and annual anti-HCV testing is recommended. HCV-PCR should be considered at baseline for persons with HCV risk factors, and for returning travellers who received dialysis in HCV-endemic countries to identify HCV infection occurring outside the hemodialysis unit.

scholarly journals Hepatitis C Virus Infection and Genotypes in Chronic Hemodialysis Patients in Kinshasa: Prevalence and Risk Factors

2021 ◽  
Author(s):  
Mathieu Muna Ngilibuma ◽  
Vieux Momeme Mokoli ◽  
Yannick Mayamba Nlandu ◽  
Yannick Mompango Engole ◽  
Cedric Kabemba Ilunga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hemodialysis Patients ◽  
Chronic Hemodialysis ◽  
Hcv Infection ◽  
Sub Saharan Africa ◽  
Steady Increase ◽  
Genotype 4 ◽  
Genotype 2

Abstract IntroductionThe steady increase in the number of chronic hemodialysis patients in sub-Saharan Africa (SSA) calls for improved management of those patients. The present study aimed to determine the frequency of hepatitis C virus (HCV) infection, the prevalent genotypes and the risk factors associated with HCV in hemodialysis patients in Kinshasa (DR Congo). MethodsA cross sectional study was conducted from February to June 2018 in all hemodialysis centers in Kinshasa. Blood samples were collected from 127 chronic hemodialysis patients and tested for the presence of antibodies against HCV. The HCV genotype was identified by real time polymerase chain reaction (RT- PCR). ResultsTwenty-two (17.3 %) patients were anti-HCV positive, ranging from 0 % to 52.9 % in different centers. Genotype 4 was detected in 18/22 (81.8 %), followed by genotype 2 in 2/22 (9.1%), and both genotypes 2 and 4 in one patient (4.5%). One patient had an undetermined genotype (4.5 %). Having received at least 4 transfusions [7,21 (1,09-10,61); p=0.040)], not being under EPO treatment [5,81(1,47-12,96); p=0.012)], being on hemodialysis for at least 14 months [3,63(1,60-5,05); p=0.035)]and being dialyzed in an overloaded center [2,06(0,83-5,86); p=0.073)] were associated with a greater risk of HCV infection.ConclusionThis study highlights the importance of strategies to prevent HCV infection in hemodialysis patients in Kinshasa. This issue is important for SSA countries which are facing several economic and logistical challenges.

scholarly journals Immunity in Chimpanzees Chronically Infected with Hepatitis C Virus: Role of Minor Quasispecies in Reinfection

1998 ◽  
Vol 72 (3) ◽  
pp. 1725-1730 ◽  
Author(s):  
Colby A. Wyatt ◽  
Linda Andrus ◽  
Betsy Brotman ◽  
Fannie Huang ◽  
Dong-Hun Lee ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Primary Infection ◽  
Hcv Infection ◽  
Natural Evolution ◽  
Genotype 1A ◽  
Natural Progression ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT We have previously reported that chimpanzees chronically infected with hepatitis C virus (HCV) could be reinfected, even with the original infecting strain. In this study we tested the hypothesis that this might reflect the presence of minor quasispecies to which there was little or no immunity. To evaluate this hypothesis, we sequenced multiple clones taken at intervals after primary infection and rechallenge from four chronically infected chimpanzees. The inoculum used in these studies (HCV-H, genotype 1a) revealed 17 separate variants among 46 clones sequenced. Following challenge, each of the four challenged animals showed marked alterations of their quasispecies distribution. The new variants, which appeared 1 to 6 weeks after challenge, were either identical to or closely resembled variants present in the challenge inoculum. These results, paralleled by an increase in viremia in some of the challenged animals, suggest that quasispecies in the challenge inoculum were responsible for signs of reinfection and that there was little immunity. However, the newly emerged quasispecies completely took over infection in only one animal. In the remaining three chimpanzees the prechallenge quasispecies were able to persist. The natural evolution of infection within chimpanzees resulted in variants able to compete with the inoculum variants. Whether through reexposure or the natural progression of infection, newly emerged quasispecies are likely to play a role in the pathogenesis of chronic HCV infection.

scholarly journals A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus

2020 ◽  
Author(s):  
Candelaria Vergara ◽  
Ana Valencia ◽  
Chloe L Thio ◽  
James J Goedert ◽  
Alessandra Mangia ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Ribosomal Protein ◽  
X Chromosome ◽  
Genome Wide Association Study ◽  
Vaccine Development ◽  
Hcv Infection ◽  
Spontaneous Clearance ◽  
Acute Hepatitis C ◽  
Septin 6

Abstract Background Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors. Methods To identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group. Results A male-specific region near the adenosine diphosphate–ribosylation factor–like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10−07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10−06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor. Conclusions These novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

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