Co-replication analyses of naturally occurring defective hepatitis B virus variants with wild-type.
Complex hepatitis B virus (HBV) variants with mutations in core promoter (Cp) plus deletions in the C gene and/or preS region--that are associated with development of liver cirrhosis in renal transplant recipients--show a drastically changed phenotype with altered transcription and disturbed surface and core protein expression. Here, we analyzed the replication phenotype of six different defective variant genomes, isolated from two patients, after co-transfection with HBV wild-type (wt) in varying proportions. Both in HuH7 and HepG2 cells, the variants showed enhanced replication and enrichment in the different transfected variant-wt mixtures. Contrary to artificial variants with only C gene deletions in wt context, the original complex variants as well as wt genomes carrying C gene and Cp mutations of the variants did mostly not suppress wt replication. Thus, the Cp mutations compensate the suppression of wt by C gene deletions and furthermore enhance the replication level.
Märschenz
Stefanie
S
Institut für Virologie (Helmut-Ruska-Haus), Charité-Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany. stefanie.maerschenz@charite.de
Brinckmann
Anja
A
Nürnberg
Peter
P
Krüger
Detlev H
DH
Günther
Stephan
S
Meisel
Helga
H
D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D006509:Hepatitis B / Q000635:transmission / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects; D009154:Mutation / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
D004279:DNA, Viral; D011994:Recombinant Proteins; D014764:Viral Proteins