Unusual naturally occurring humoral and cellular mutated epitopes of Hepatitis B virus in a chronically infected Argentine patient with anti-HBs antibodies.

MARÍA L. CUESTAS, VERÓNICA L. MATHET, VANESA RUIZ, MARÍA L. MINASSIAN , CINTIA RIVERO , ANDREA SALA, DANIEL CORACH , ANALÍA. ALESSIO, MARCIA POZZATI , BERNARDO FRIDER AND JOSÉ R. OUBIÑA.

JOURNAL OF CLINICAL MICROBIOLOGY

American Society for Microbiology

Lugar: Washington DC; Año: 2006 vol. 44 p. 2191 - 2198

0095-1137

Este trabajo es el mismo que fuera presentado como Trabajo completo en las XIII Jornadas de Jóvenes Investigadores de AUGM en Setiembre 2005 (publicado en esa fecha en CD). Véase el resumen debajo de la línea. Recibió el comentario de "Excellent study" por el editor del Journal of Clinical Microbiology. ------------------------------------------------------------------------------------------------------------------ Serum Hepatitis B virus (HBV) DNA was extracted from a chronically infected patient with co-circulation of Hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies. Direct PCR and clones´ derived sequences of the S and the overlapped P genes were obtained. DNA sequences and phylogenetic analysis ascribed this isolate to genotype A (serotype adw 2). Five out of six HBV DNA clones exhibited point mutations inside and outside the major hydrophilic region (MHR), while the remaining sixth clone exhibited a genotype A “wild type” amino acid sequence. Observed replacements included both humoral and/or cellular (MHC-I and MHC-II) HBV mutated epitopes, such as S45A, P46H, L49H, C107R, T125A, M133K, I152F, P153T, T161S, G185E, A194T, G202R and I213L. None of these mutants were individually present within a given clone. The I213L replacement was the only one observed in the five clones carrying non-synonymous mutations in the S gene. Some of the amino acid substitutions are reportedly known to be responsible for the emergence of immune escape mutants. C107R replacement prevents disulfide bonding, thus disrupting the first loop of the HBs Ag. Circulation of some of these mutants may represent a potential risk for the community, since neither current hepatitis B vaccines nor hyperimmune Hepatitis B immune globulin (HBIG) are effective to prevent the liver disease thereto associated. Moreover, some of the recorded HBs Ag variants may influence the accuracy of the results obtained  with currently used diagnostic tests.