TY - JOUR
TI - Core Mutations in Patients With Acute Episodes of Chronic HBV Infection
Are Associated With the Emergence of New Immune Recognition Sites and
the Development of High IgM Anti-HBc Index Values
AU - Alexopoulou, Alexandra
AU - Baltayiannis, Gerassimos
AU - Eroglu, Cafer
AU - and Nastos, Theodoros
AU - Dourakis, Spyros P.
AU - Archimandritis,
AU - Athanasios J.
AU - Karayiannis, Peter
JO - Journal of Medical Virology
PY - 2009
VL - 81
TODO - 1
SP - 34-41
PB - Wiley-Liss, Inc.
SN - 0146-6615, 1096-9071
TODO - 10.1002/jmv.21337
TODO - acute exacerbations; HBeAg-negative patients; core variants;
quasispecies; immune epitopes
TODO - Acute exacerbations in HBeAg negative patients with chronic hepatitis 8
virus (HBV) infection are invariably associated with concurrent
increases in the index of IgM class antibodies against the core protein
(anti-HBc) of the virus. This study aimed to investigate whether this
was related to the clearance of variants from the quasispecies pool and
the appearance of new ones, with aminoacid substitutions in well
recognized B-cell epitopes. In this study, 5 HBeAg negative patients (A
to E) with 13 sequential serum samples (A1-A2, B1-B2-B3, C1-C2,
D1-D2-D3, E1-E2-E3) were investigated after amplification of the entire
core encoding region followed by cloning/sequencing studies. The
sequences at different time points were compared with those from a
single HBeAg positive patient with no apparent acute exacerbations. The
results from sequence comparison showed that virus variants emerged in
all (A2, B3, C2, D3, E2, and E3) but two (B2 and D2) subsequent sera
with amino-acid substitutions affecting B-cell epitopes. It is concluded
that the rise in the values of IgM anti-HBc may be attributed to the
alteration of the antigenic epitopes leading to new antibody production
in the majority of the cases. However, it appears that increases in IgM
anti-HBc indexes in a few cases may relate to other possible mechanisms
which are discussed. J. Med. Virol. 81:34-41, 2009. (c) 2008 Wiley-Liss,
Inc.
ER -