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Journal of Virology, March 2006, p. 2968-2975, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2968-2975.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Coexistence of Hepatitis B Surface Antigen (HBs Ag) and Anti-HBs Antibodies in Chronic Hepatitis B Virus Carriers: Influence of "a" Determinant Variants

Olivier Lada,1 Yves Benhamou,2 Thierry Poynard,2 and Vincent Thibault1*

Departments of Virology,1 Hepato-Gastro-Enterology, AP-HP Pitie-Salpetriere Hospital, Paris, France2

Received 9 May 2005/ Accepted 2 December 2005

In chronic hepatitis B (CHB), the persistence of hepatitis B surface antigen (HBs Ag) is sometimes associated with antibodies (Ab) to HBs (anti-HBs). To assess the hypothesis of the selection of HBs Ag immune escape variants in CHB patients, the variability of the HBV S gene was determined for patients persistently carrying both HBs Ag and anti-HBs antibodies and patients solely positive for HBs Ag. We selected 14 patients who presented both markers (group I) in several consecutive samples and 12 patients positive for HBs Ag only (group II). The HBs Ag-encoding gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed. The number of residue changes within the S protein was 2.7 times more frequent for group I than for group II patients and occurred mostly in the "a" determinant of the major hydrophilic region (MHR), with 9.52 versus 2.43 changes per 100 residues (P = 0.009), respectively. Ten patients (71%) from group I, but only three (25%) from group II, presented at least two residue changes in the MHR. The most frequent changes in group I patients were located at positions s145, s129, s126, s144, and s123, as described for immune escape variants. In CHB patients, the coexistence of HBs Ag and anti-HBs Ab is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process with regard to vaccine efficacy, diagnosis, and clinical evolution remain partially unknown.

* Corresponding author. Mailing address: Virology-CERVI, 83 Bd. de l'Hopital, 75651 Paris Cedex, France. Phone: 33-1 42 17 74 26. Fax: 33-1 42 17 74 11. E-mail: vincent.thibault{at}psl.ap-hop-paris.fr.

Journal of Virology, March 2006, p. 2968-2975, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2968-2975.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hoa, P. T. L., Huy, N. T., Thu, L. T., Nga, C. N., Nakao, K., Eguchi, K., Chi, N. H., Hoang, B. H., Hirayama, K. (2009). Randomized Controlled Study Investigating Viral Suppression and Serological Response following Pre-S1/Pre-S2/S Vaccine Therapy Combined with Lamivudine Treatment in HBeAg-Positive Patients with Chronic Hepatitis B. Antimicrob. Agents Chemother. 53: 5134-5140 [Abstract] [Full Text]  


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