Preferential ribosomal scanning is involved in the differential synthesis of the hepatitis B viral surface antigens from subgenomic transcripts.
The envelope of the hepatitis B virus (HBV) is composed of three species of proteins, the large (L), middle (M), and major (S) surface proteins (HBsAgs), each of different molecular weights but sharing a common C-terminus. These three HBsAgs, encoded by two species of viral subgenomic transcripts (2.1 and 2.4 kb), which have a heterogenous 5'-terminus, appear in different amounts in both the 42-nm virions and the 22-nm subviral particles. To investigate the involvement of translational control in the differential expression of the L, M, and S proteins, we tested the translational capability of 2.1- and 2.4-kb transcripts in in vitro translation and of 2.1-kb transcripts in in vivo transfection experiments. Results of in vitro translation indicated that a large amount of the L protein and a very small amount of the M and S proteins were synthesized from the 2.4-kb mRNA. Translation of the 2.1-kb mRNA resulted in a 4:1 ratio of the S protein to the M protein. In contrast, translation of a similar 2.1-kb mRNA containing an optimal initiation context (5'-ACCATGG-3') of the pre-S2 region resulted in a reversed ratio, four times as much M protein as S protein. This result was also obtained by transfection of hepatoma cells with plasmid DNAs containing the mutated sequence (5'-ACCATGG-3') of the pre-S2 region. In considering these results, the production of a large amount of the L protein from the 2.4-kb mRNA and the determination of the level of the M protein by the context of translational initiation, we suggest that a preferential translational initiation is involved in the expression of differential amounts of the L, M, and S proteins.
Sheu
S Y
SY
Graduate Institute of Microbiology and Immunology, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China.
Lo
S J
SJ
D001483:Base Sequence; D003062:Codon; D004279:DNA, Viral; D015967:Gene Expression Regulation, Viral; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism*; D014158:Transcription, Genetic
D003062:Codon; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens