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.

scholarly journals The natural history of early hepatitis C virus evolution; lessons from a global outbreak in human immunodeficiency virus-1-infected individuals

2011 ◽  
Vol 92 (10) ◽  
pp. 2227-2236 ◽  
Author(s):  
Emma C. Thomson ◽  
Jennifer A. Smith ◽  
Paul Klenerman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell Response ◽  
Hcv Infection ◽  
Hiv Positive ◽  
Spontaneous Clearance ◽  
Acute Hepatitis C ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1

New insights into the early viral evolution and cellular immune response during acute hepatitis C virus (HCV) infection are being gained following a global outbreak in human immunodeficiency virus-1 (HIV)-positive men who have sex with men. Cross-sectional and longitudinal sequence analysis at both the population and individual level have facilitated tracking of the HCV epidemic across the world and enabled the development of tests of viral diversity in individual patients in order to predict spontaneous clearance of HCV and response to treatment. Immunological studies in HIV-positive cohorts have highlighted the role of the CD4+ T-cell response in the control of early HCV infection and will increase the opportunity for the identification of protective epitopes that could be used in future vaccine development.

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 PD-1 Expression in Acute Hepatitis C Virus (HCV) Infection Is Associated with HCV-Specific CD8 Exhaustion

2006 ◽  
Vol 80 (22) ◽  
pp. 11398-11403 ◽  
Author(s):  
Simona Urbani ◽  
Barbara Amadei ◽  
Daniela Tola ◽  
Marco Massari ◽  
Simona Schivazappa ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Function ◽  
Hcv Infection ◽  
Acute Hepatitis C ◽  
Inhibitory Receptor ◽  
Cd8 Cells ◽  
Acute Hcv ◽  
Cd8 Cell ◽  
Acute Hcv Infection

ABSTRACT Hepatitis C virus (HCV)-specific CD8 cell exhaustion may represent a mechanism of HCV persistence. The inhibitory receptor PD-1 has been reported to be up-regulated in exhausted CD8 cells. Therefore, we studied PD-1 expression longitudinally during acute HCV infection. Most HCV-specific CD8 cells expressed PD-1 at the time of acute illness, irrespective of the final outcome. PD-1 expression declined with the acquisition of a memory phenotype and recovery of an efficient CD8 cell function in resolving HCV infections, whereas high levels were maintained when HCV persisted and HCV-specific CD8 cells remained dysfunctional. Blocking PD-1/PDL-1 interaction with an anti-PDL-1 antibody improved the capacity of expansion of virus-specific CD8 cells.

scholarly journals Hepatitis C virus infection in HIV-infected men who have sex with men: sustained rising incidence in Antwerp, Belgium, 2001–2009

2010 ◽  
Vol 15 (39) ◽  
Author(s):  
E Bottieau ◽  
L Apers ◽  
M Van Esbroeck ◽  
M Vandenbruaene ◽  
E Florence
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Hiv Positive ◽  
Acute Hepatitis C ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Awareness Campaigns ◽  
Rising Incidence ◽  
Sex With Men

During the last decade, outbreaks of acute hepatitis C virus (HCV) infection have been reported among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) in several European countries. To study this emerging infection in MSM in Antwerp, Belgium, we reviewed all cases of newly acquired HCV infection in HIV-positive MSM followed from 2001 to 2009 at the HIV/sexually transmitted infection (STI) reference clinic of the Institute of Tropical Medicine in Antwerp. Newly acquired HCV infection was considered as certain or probable according to local definitions. During the study period, 69 episodes of newly acquired HCV infection (40 certain and 29 probable) were diagnosed in 67 HIV-infected MSM. In only 10 episodes (14%) were the patients symptomatic. The annual incidence of HCV infection in our population of HIV-infected MSM rose steadily from 0.2% in 2001 to 1.51% in 2008, and then peaked to 2.9% in 2009. For 60 episodes (87%), another STI (mainly syphilis and lymphogranuloma venereum) had been diagnosed within the six months before the diagnosis of HCV infection. All but one patient with available genotyping (n=54) were found to be infected with the difficult-to-treat HCV genotypes 1 or 4. Our results therefore demonstrate the rising incidence of HCV infection in HIV-positive MSM in Antwerp, since 2001, which reached an alarming level in 2009. Targeted awareness campaigns and routine screening are urgently needed to limit further HCV spread and its expected long-term consequences.

scholarly journals Convergent antibody responses associated with broad neutralization of hepatitis C virus and clearance of infection

2021 ◽  
Author(s):  
Nicole E. Skinner ◽  
Clinton O. Ogega ◽  
Nicole Frumento ◽  
Kaitlyn E. Clark ◽  
Srinivasan Yegnasubramanian ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Early Development ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Plasma ◽  
Spontaneous Clearance ◽  
Cell Repertoire ◽  
Molecular Features

AbstractEarly development of broadly neutralizing antibodies (bNAbs) targeting the hepatitis C virus (HCV) envelope glycoprotein E2 is associated with spontaneous clearance of infection, so induction of bNAbs is a major goal of HCV vaccine development. However, much remains to be learned at a molecular level about protective E2-reactive antibodies, since HCV infection persists in some individuals despite early development of broadly neutralizing plasma. To examine B cell repertoire features associated with broad neutralization and viral clearance, we performed RNA sequencing of the B cell receptors (BCRs) of HCV E2-reactive B cells of people with cleared or persistent HCV, including subjects with high or low plasma neutralizing breadth in both clearance and persistence groups. We identified many E2-reactive public BCR clonotypes, which are antibody clones with the same V and J-genes and identical CDR3 sequences, shared among subjects grouped by either clearance or neutralization status. The majority (89) of these public clonotypes were shared by two subjects with broad plasma neutralizing activity and cleared infection, but not found in subjects with high plasma neutralizing breadth and persistent infection. We cloned a potent, cross-reactive neutralizing monoclonal antibody (mAb) by pairing the most abundant public heavy and light chains from these two subjects, providing evidence that broadly E2-reactive public clonotypes arise in a subset of individuals with broadly neutralizing plasma and spontaneous clearance of infection. Further characterization of the molecular features and function of these antibodies can inform HCV vaccine development.

1063 FACTORS ASSOCIATED WITH SPONTANEOUS CLEARANCE DURING ACUTE HEPATITIS C VIRUS INFECTION

2010 ◽  
Vol 52 ◽  
pp. S411 ◽  
Author(s):  
J. Grebely ◽  
G.J. Dore ◽  
M. Schim van der Loeff ◽  
A.L. Cox ◽  
J. Bruneau ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Acute Hepatitis ◽  
Spontaneous Clearance ◽  
Acute Hepatitis C ◽  
Hepatitis C Virus Infection ◽  
Factors Associated

scholarly journals Testing Strategy To Identify Cases of Acute Hepatitis C Virus (HCV) Infection and To Project HCV Incidence Rates

2007 ◽  
Vol 46 (2) ◽  
pp. 499-506 ◽  
Author(s):  
K. Page-Shafer ◽  
B. L. Pappalardo ◽  
L. H. Tobler ◽  
B. H. Phelps ◽  
B. R. Edlin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Acute Hepatitis ◽  
Incidence Rates ◽  
Hcv Infection ◽  
Acute Hepatitis C ◽  
Testing Strategy

scholarly journals HLA-Cw*04 and Hepatitis C Virus Persistence

2002 ◽  
Vol 76 (10) ◽  
pp. 4792-4797 ◽  
Author(s):  
Chloe L. Thio ◽  
Xiaojiang Gao ◽  
James J. Goedert ◽  
David Vlahov ◽  
Kenrad E. Nelson ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Persistence ◽  
Human Leukocyte ◽  
Hcv Infection ◽  
Class I ◽  
Hcv Rna ◽  
Acute Hepatitis C ◽  
Strong Linkage Disequilibrium ◽  
Persistently Infected

ABSTRACT In studies of acute hepatitis C virus (HCV) infection, the early host immune response is one of the determinants of viral persistence. The class I human leukocyte antigens (HLA), which present foreign antigen to cytolytic T cells, are integral components of this response. We hypothesized that the highly polymorphic HLA genes affect the outcome of an HCV infection. To test this hypothesis, we molecularly typed 231 persons with well-documented clearance of an HCV infection and 444 matched persistently infected persons. HLA-A*1101 (odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.27 to 0.89), HLA-B*57 (OR, 0.62; 95% CI, 0.39 to 1.00), and HLA-Cw*0102 (OR, 0.43; 95% CI, 0.21 to 0.89) were associated with viral clearance, whereas HLA-A*2301 (OR, 1.78; 95% CI, 1.01 to 3.11) and HLA-Cw*04 (OR, 1.78; 95% CI, 1.21 to 2.59) were associated with viral persistence. HLA-Cw*04 is in strong linkage disequilibrium with HLA-B*53 and HLA-B*35, but only HLA-B*53 (OR, 1.70; 95% CI, 0.95 to 3.06) and the Cw*04-B*53 haplotype (OR, 1.76; 95% CI, 0.94 to 3.26) were weakly associated with viral persistence. HLA-B*53 has similar, but not necessarily identical, binding specificity to some HLA-B*35 subtypes (B*35-Px group). The association with the B*35-Px group was less strong than with HLA-B*53 alone. The association of HLA-Cw*04 with HCV persistence was codominant (two copies of the gene were more strongly associated with persistence than one copy). However, HLA-Cw*04 was not associated with HCV RNA levels among the persistently infected individuals. Since Cw*04 is a ligand for the killer immunoglobulin-like receptors on natural killer cells, these cells may be involved in recovery from HCV infection. Further investigation is needed to understand the relationship between class I alleles and HCV clearance.

scholarly journals Acute hepatitis C virus infection

2008 ◽  
Vol 13 (21) ◽  
Author(s):  
W L Irving ◽  
D Salmon ◽  
C Boucher ◽  
I M Hoepelman
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Acute Hepatitis C ◽  
Acute Hcv ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
The Individual ◽  
Acute Hcv Infection ◽  
Subsequent Risk

Around 25% of people infected with hepatitis C virus (HCV) are able to clear the infection spontaneously, while the majority become chronically infected, with a subsequent risk for the individual patient of progressive inflammatory liver disease, cirrhosis, hepatocellular carcinoma and liver-related death (Figure 1). Much is known about the epidemiology, pathogenesis, diagnosis and management of chronic HCV infection. In comparison, knowledge about acute HCV infection is patchy. In this article, we will highlight concerns relating to acute HCV infection and suggest that public health bodies responsible for managing the HCV epidemic should redirect at least some of their resources to dealing with these issues.

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