Pre-S deletion mutants co-exist with wild-type virus at low viral replication stage in Singapore chronic hepatitis B virus carriers

摘要

Changes in the hepatitis B virus (HBV) genome have frequently been found during chronic viral infection. These changes include mutations and deletions within or outside the coding regions for HBV viral proteins and have various clinical consequences [1]. Mutations occurring on the major HBV surface antigen (HBsAg) can result in changes in viral antigenicities [3], and those located in the catalytic domain of the HBV DNA polymerase have been associated with HBV resistance to antiviral therapy [14]. In addition to the deletions in the core promoter that affect the viral replication [4], deletions in the pre-S region have also been reported [2, 7, 9, 12, 13]. The pre-S region is in the same coding frame of the major HBsAg and has two components: pre-Si and pre-S2 with 119 and 55 amino acids (aa) respectively [1]. Several important domains have been identified in the pre-S region including the promoter for the major HB-sag [10], epitopes for T or B cells [6], and attachment site of HBV to hepatocytes [8]. Deletions in the pre-S region are, therefore, expected to alter the synthesis of HBsAg, to result in chronic infection owing to mutants capable of escaping immune surveillance, and to affect viral replication.