Hepatitis B virus genomes from long-term immunosuppressed virus carriers are modified by specific mutations in several regions

There is increasing evidence that hepatitis B virus (HBV) infection of an i mmunosuppressed host is associated with the appearance of virus mutants. To characterize the virus circulating in patients in detail, eleven full-leng th HBV genomes, isolated from the serum of five highly viraemic renal trans plant recipients with liver disease, were cloned and sequenced. The genomes contained deletions in the C gene, deletions in the pre-Silt region freque ntly removing the pre-St initiation codon, premature termination codons in the pre-Si or S region, and/or deletions/insertions in the X gene/core prom oter. The mutations occurred at different positions and in various combinat ions; even mutant genomes circulating within a patient differed strikingly. It is concluded that long-term immunosuppression is associated with the oc currence of heterogeneous populations of partially defective HBV characteri zed by a specific mutation pattern. Efficient intracellular trans-complemen tation probably enables high virus replication in vivo.