Association of killer cell immunoglobulin-like receptors with spontaneous clearance of hepatitis C virus in the Chinese population

Transfusion ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 1028-1035 ◽  
Author(s):  
Zhengang Shan ◽  
Jieting Huang ◽  
Qiao Liao ◽  
Ke Huang ◽  
Min Wang ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chinese Population ◽  
Killer Cell ◽  
Spontaneous Clearance

Spontaneous Clearance of HCV in HIV–Hepatitis C Virus Coinfected Liver Transplant Patients: Prospective Study

2012 ◽  
Vol 44 (7) ◽  
pp. 2100-2102 ◽  
Author(s):  
M. Gutiérrez-Moreno ◽  
C. Bernal-Bellido ◽  
G. Suárez-Artacho ◽  
J.M. Álamo-MartÍnez ◽  
L.M. Marín-Gómez ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Prospective Study ◽  
Liver Transplant ◽  
Spontaneous Clearance ◽  
Transplant Patients

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.

scholarly journals Escape from HLA-B*08-Restricted CD8 T Cells by Hepatitis C Virus Is Associated with Fitness Costs

2008 ◽  
Vol 82 (23) ◽  
pp. 11803-11812 ◽  
Author(s):  
Shadi Salloum ◽  
Cesar Oniangue-Ndza ◽  
Christoph Neumann-Haefelin ◽  
Laura Hudson ◽  
Silvia Giugliano ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Replication ◽  
Consensus Sequence ◽  
Acute Infection ◽  
Spontaneous Clearance ◽  
Fitness Costs ◽  
Genotype 1B ◽  
The Impact

ABSTRACT The inherent sequence diversity of the hepatitis C virus (HCV) represents a major hurdle for the adaptive immune system to control viral replication. Mutational escape within targeted CD8 epitopes during acute HCV infection has been well documented and is one possible mechanism for T-cell failure. HLA-B*08 was recently identified as one HLA class I allele associated with spontaneous clearance of HCV replication. Selection of escape mutations in the immunodominant HLA-B*08-restricted epitope HSKKKCDEL1395-1403 was observed during acute infection. However, little is known about the impact of escape mutations in this epitope on viral replication capacity. Their previously reported reversion back toward the consensus residue in patients who do not possess the B*08 allele suggests that the consensus sequence in this epitope is advantageous for viral replication in the absence of immune pressure. The aim of this study was to determine the impact of mutational escape from this immunodominant epitope on viral replication. We analyzed it with a patient cohort with chronic HCV genotype 1b infection and in a single-source outbreak (genotype 1b). Sequence changes in this highly conserved region are rare and selected almost exclusively in the presence of the HLA-B*08 allele. When tested in the subgenomic replicon (Con1), the observed mutations reduce viral replication compared with the prototype sequence. The results provide direct evidence that escape mutations in this epitope are associated with fitness costs and that the antiviral effect of HLA-B*08-restricted T cells is sufficiently strong to force the virus to adopt a relatively unfavorable sequence.

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