PMID- 25720337
OWN - NLM
STAT- MEDLINE
DCOM- 20150916
LR  - 20150625
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 62
IP  - 1
DP  - 2015 Jul
TI  - Adaptation of the hepatitis B virus core protein to CD8(+) T-cell selection 
      pressure.
PG  - 47-56
LID - 10.1002/hep.27771 [doi]
AB  - Activation of hepatitis B virus (HBV)-specific CD8 T cells by therapeutic 
      vaccination may promote sustained control of viral replication by clearance of 
      covalently closed circular DNA from infected hepatocytes. However, little is 
      known about the exact targets of the CD8 T-cell response and whether HBV 
      reproducibly evades CD8 T-cell immune pressure by mutation. The aim of this study 
      was to address if HBV reproducibly selects substitutions in CD8 T-cell epitopes 
      that functionally act as immune escape mutations. The HBV core gene was amplified 
      and sequenced from 148 patients with chronic HBV infection, and the human 
      leukocyte antigen (HLA) class I genotype (A and B loci) was determined. Residues 
      under selection pressure in the presence of particular HLA class I alleles were 
      identified by a statistical approach utilizing the novel analysis package 
      SeqFeatR. With this approach we identified nine residues in HBV core under 
      selection pressure in the presence of 10 different HLA class I alleles. 
      Additional immunological experiments confirmed that seven of the residues were 
      located inside epitopes targeted by patients with chronic HBV infection carrying 
      the relevant HLA class I allele. Consistent with viral escape, the selected 
      substitutions reproducibly impaired recognition by HBV-specific CD8 T cells. 
      CONCLUSION: Viral sequence analysis allows identification of HLA class 
      I-restricted epitopes under reproducible selection pressure in HBV core; the 
      possibility of viral escape from CD8 T-cell immune pressure needs attention in 
      the context of therapeutic vaccination against HBV.
CI  - (c) 2015 by the American Association for the Study of Liver Diseases.
FAU - Kefalakes, Helenie
AU  - Kefalakes H
AD  - Institute of Virology, University of Duisburg-Essen, University Hospital, Essen, 
      Germany.
AD  - Department of Gastroenterology and Hepatology, University of Duisburg-Essen, 
      University Hospital, Essen, Germany.
FAU - Budeus, Bettina
AU  - Budeus B
AD  - Research Group Bioinformatics, Centre for Medical Biotechnology, University of 
      Duisburg-Essen, Essen, Germany.
FAU - Walker, Andreas
AU  - Walker A
AD  - Institute of Virology, University of Duisburg-Essen, University Hospital, Essen, 
      Germany.
FAU - Jochum, Christoph
AU  - Jochum C
AD  - Department of Gastroenterology and Hepatology, University of Duisburg-Essen, 
      University Hospital, Essen, Germany.
FAU - Hilgard, Gudrun
AU  - Hilgard G
AD  - Department of Gastroenterology and Hepatology, University of Duisburg-Essen, 
      University Hospital, Essen, Germany.
FAU - Heinold, Andreas
AU  - Heinold A
AD  - Institute for Transfusion Medicine, University of Duisburg-Essen, University 
      Hospital, Essen, Germany.
FAU - Heinemann, Falko M
AU  - Heinemann FM
AD  - Institute for Transfusion Medicine, University of Duisburg-Essen, University 
      Hospital, Essen, Germany.
FAU - Gerken, Guido
AU  - Gerken G
AD  - Department of Gastroenterology and Hepatology, University of Duisburg-Essen, 
      University Hospital, Essen, Germany.
FAU - Hoffmann, Daniel
AU  - Hoffmann D
AD  - Research Group Bioinformatics, Centre for Medical Biotechnology, University of 
      Duisburg-Essen, Essen, Germany.
FAU - Timm, Joerg
AU  - Timm J
AD  - Institute for Virology, Heinrich-Heine-University, University Hospital, 
      Duesseldorf, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150325
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Viral Core Proteins)
SB  - IM
MH  - Adaptation, Biological
MH  - CD8-Positive T-Lymphocytes/*physiology
MH  - Epitopes, T-Lymphocyte
MH  - *Genes, MHC Class I
MH  - Hepatitis B virus/*genetics
MH  - Hepatitis B, Chronic/immunology/virology
MH  - Humans
MH  - *Selection, Genetic
MH  - Viral Core Proteins/*genetics
EDAT- 2015/02/28 06:00
MHDA- 2015/09/17 06:00
CRDT- 2015/02/28 06:00
PHST- 2014/10/27 00:00 [received]
PHST- 2015/02/25 00:00 [accepted]
PHST- 2015/02/28 06:00 [entrez]
PHST- 2015/02/28 06:00 [pubmed]
PHST- 2015/09/17 06:00 [medline]
AID - 10.1002/hep.27771 [doi]
PST - ppublish
SO  - Hepatology. 2015 Jul;62(1):47-56. doi: 10.1002/hep.27771. Epub 2015 Mar 25.