Functional surfaces of the hepatitis B virus capsid.
The hepatitis B virus (HBV) core protein (CP) forms the shell of an icosahedral nucleocapsid. In a former work, we identified 11 amino acid residues of CP exposed on the capsid surface by an alanine mutation scan as being important for capsid envelopment. We now introduced several other amino acids at six of these positions and found that almost all 27 tested point mutations at S17, K96, and I126 reproduced the phenotype of the alanine mutation (with only two exceptions): the formation of nucleocapsids and of the viral DNA genome was wild type, but capsid envelopment and virion release were strongly inhibited. This indicates that these side chains have a very specific function during nucleocapsid envelopment. We also identified several CP point mutations (e.g., F122V/S/Y and R127D/G) allowing the formation of capsids but preventing the packaging of pregenomic RNA. The envelopment of such mutant capsids was blocked. Apparently, these CP mutations hampered the recognition/packaging of the pregenome-P-protein complex by CP, a process which is still barely understood, and the mutant capsids devoid of HBV-specific nucleic acid did not express the capsid maturation signal required for envelopment.
Pairan
Alexander
A
Department of Virology, University of Göttingen, Kreuzbergring 57, D-37075 Göttingen, Germany.
Bruss
Volker
V
D002213:Capsid / Q000502:physiology; D036022:Capsid Proteins / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016297:Mutagenesis, Site-Directed; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014771:Virion / Q000235:genetics; D019065:Virus Assembly / Q000235:genetics
D036022:Capsid Proteins; D004279:DNA, Viral; D012367:RNA, Viral