Intracellular distribution of hepatitis B virus core protein expressed in vitro depends on the sequence of the isolate and the serologic pattern.
Intracellular localization of hepatitis B core antigen (HBcAg) in vivo varies with liver cell damage. Localization of HBcAg was studied using transfection of cloned HBcAg variants. Twenty-six samples were obtained from 14 patients with liver disease; 10 were hepatitis B e antigen positive, and 16 were anti-hepatitis B e (HBe) positive. In hepatitis B e antigen (HBeAg)-positive patients, HBcAg predominantly localized in the nucleus; in anti-HBe-positive patients, it accumulated mainly in the cytoplasm. Of the 13 samples with nuclear localization, 9 were HBeAg positive; 5 of 13 had C-terminus and/or B cell epitope mutations. All but 1 of the 13 samples with predominantly cytoplasmic localization were anti-HBe positive; all 13 had mutations. Reversion of mutant sequences with cytoplasmic expression back to the wild type led to a shifting back to nuclear distribution. Thus, the pattern of HBcAg localization in vitro depends on sequence and the serologic pattern of chronic infection, paralleling the situation in vivo.
Jazayeri
S Mohammed
SM
Division of Virology, Institute of Biomedical and Life Science, University of Glasgow, Glasgow, Scotland.
Jazayeri
Mohammed S
MS
Dornan
Edward S
ES
Boner
Winifred
W
Fattovich
Giovanna
G
Hadziyannis
Stephanos
S
Carman
William F
WF
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000821:virology*; D003593:Cytoplasm / Q000821:virology*; D014644:Genetic Variation; D006509:Hepatitis B / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood*; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006513:Hepatitis B e Antigens / Q000276:immunology / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D008107:Liver Diseases / Q000821:virology; D009154:Mutation; D016133:Polymerase Chain Reaction; D014162:Transfection
D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens