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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
Author(s) -
Alexopoulou Alexandra,
Baltayiannis Gerassimos,
Eroglu Cafer,
Nastos Theodoros,
Dourakis Spyros P.,
Archimandritis Athanasios J.,
Karayiannis Peter
Publication year - 2009
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21337
Subject(s) - viral quasispecies , epitope , virology , antibody , virus , hepatitis b virus , immunology , medicine , immune system , immunoglobulin m , biology , antigen , hbeag , hepatitis c virus , hbsag , immunoglobulin g
Abstract Acute exacerbations in HBeAg negative patients with chronic hepatitis B 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. © 2008 Wiley‐Liss, Inc.