Expression, assembly competence and antigenic properties of hepatitis B virus core gene deletion variants from infected liver cells

Previous studies have shown that the progression of hepatitis B virus-relat ed liver disease in long-term immunosuppressed kidney transplant recipients is associated with the accumulation of virus variants carrying in-frame de letions in the central part of the core gene. A set of naturally occurring core protein variants was expressed in Escherichia coil in order to investi gate their stability and assembly competence and to characterize their anti genic and immunogenic properties, In addition, a library of core gene varia nts generated in vitro with deletions including the major immunodominant re gion (MIR) of the core protein was investigated. The position and length of deletions determined the behaviour of mutant core proteins in E. coli and their assignment to one of the three groups: (i) assembly-competent, (ii) s table but assembly-incompetent and (iii) unstable proteins. in vivo core va riants with MIR deletions between amino acids 77 and 93 belong to the first group. Only proteins with the shortest deletion (amino acids 86-93) showed stability and self-assembly at the same level as wild-type cores, and they showed reduced antigenicity and immunogenicity, Mutants with deletions ext ending N-terminally beyond residue G73 or C-terminally beyond G94 were foun d to be assembly-incompetent. We suggest that G73 and G94 are involved in t he folding and the native assembly of core molecules, whereas the interveni ng sequence determines the antibody response. Depending on their ability to form stable proteins or to assemble into particles, core mutants could con tribute to liver cell pathogenesis in different ways.