Identification of a novel surface mutant of hepatitis B virus in a seronegative chronic liver disease patient

Hepatitis B virus (HBV) with mutations in the envelope proteins can emerge during natural infections, vaccinations or interferon therapy and appears occasionally to escape virus elimination or detection. The implications of such mutations at the molecular level are often obscure. We report the identification of a new surface mutant of HBV. This mutant was identified, and isolated from a chronic liver disease patient, negative for HBsAg as well as other serological markers but positive for HBV DNA. Several mutations were observed in the surface antigen gene out of which a Thr118-Ala118 change was predicted to have a destabilizing effect on the structural integrity of the 'a' determinant and also alter the antigenicity profile of the mutant HBsAg. Besides a RNA hairpin loop was predicted for the transcript generated by the small surface protein of this mutant, which could have an inhibitory effect at the translational level. These observations thus indicate that mutations in the surface gene could lead to a considerable decrease or complete absence of properly folded surface antigen which in turn could explain the absence of reactive HBsAg in the serum of the patient. (C) 1999 Elsevier Science B.V. All rights reserved.