Proteasomal degradation of core protein variants from chronic hepatitis B patients.
The accumulation of complex hepatitis B virus (HBV) variants with internal in-frame deletions in the C gene in immunosuppressed renal transplant recipients is associated with a severe course of the infection leading to end-stage liver disease (ESLD). A set of six HBV C genes with internal in-frame deletions corresponding to the pattern of HBV population in immunosuppressed patients has been expressed in two different eukaryotic cell lines. Synthesis and proteasomal degradation of HBV core (HBc) protein variants were compared with those of the wild-type HBc. In all cases, the steady-state level of internally deleted HBc proteins, predominantly with longer deletions, were considerably lower and turnover was significantly higher in comparison with those of the wild-type HBc, since all deletion variants were degraded rapidly via the proteasome pathway. Involvement and consequences of the proteasomal degradation machinery in the HBc protein turnover during HBV infection with complex HBV variants in the immunosuppressed patients are discussed.
Braun
Sabine
S
Universitätsmedizin Berlin, Charité, Institut für Virologie, Campus Mitte, Charitéplatz 1, Berlin, Germany.
Zajakina
Anna
A
Aleksejeva
Jekaterina
J
Sharipo
Anatoly
A
Bruvere
Ruta
R
Ose
Velta
V
Pumpens
Paul
P
Garoff
Henrik
H
Meisel
Helga
H
Kozlovska
Tatyana
T
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D000939:Epitopes; D005814:Genes, Viral; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics* / Q000648:ultrastructure; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D016867:Immunocompromised Host; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection
D000939:Epitopes; D006512:Hepatitis B Core Antigens; D046988:Proteasome Endopeptidase Complex