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 immunosuppressed host is associated with the appearance of virus mutants. To characterize the virus circulating in patients in detail, eleven full-length HBV genomes, isolated from the serum of five highly viraemic renal transplant recipients with liver disease, were cloned and sequenced. The genomes contained deletions in the C gene, deletions in the pre-S1/2 region frequently removing the pre-S2 initiation codon, premature termination codons in the pre-S1 or S region, and/or deletions/insertions in the X gene/core promoter. The mutations occurred at different positions and in various combinations; even mutant genomes circulating within a patient differed strikingly. It is concluded that long-term immunosuppression is associated with the occurrence of heterogeneous populations of partially defective HBV characterized by a specific mutation pattern. Efficient intracellular trans-complementation probably enables high virus replication in vivo.
Preikschat
Petra
P
Institut für Medizinische Virologie der Charité, Humboldt-Universit ät zu Berlin, 10098 Berlin, Germany 1.
Meisel
Helga
H
Institut für Medizinische Virologie der Charité, Humboldt-Universit ät zu Berlin, 10098 Berlin, Germany 1.
Will
Hans
H
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, 20251 Hamburg, Germany 2.
Günther
Stephan
S
Bernhard-Nocht-Institut für Tropenmedizin, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany 3.
D001483:Base Sequence; D002353:Carrier State / Q000821:virology*; D004279:DNA, Viral; D016679:Genome, Viral; D006509:Hepatitis B / Q000276:immunology / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016867:Immunocompromised Host; D016030:Kidney Transplantation; D008969:Molecular Sequence Data; D009154:Mutation; D013997:Time Factors
D004279:DNA, Viral