Viral Protein Synthesis

Hepatitis B Virus has four promoters that produce four classes of proteins from overlapping genes (three in avian hepadnaviruses).

The Core gene (C) gives raise to two products called pre-core and core. 

The Polymerase gene (P) gives rise reverse transcriptase, RNase H, and DNA polymerase properties.

The Surface protein gene gives raise to  three proteins called preS1, preS2, and S. 

The X gene gives raise to a product that helps upregulate transcription of viral DNA.

Caption: -strand is outer strand. Shorter +strand is on inside. DR1 and DR2 are repeated elements. Other blacks boxes refer to promoters/enhancers.  Dashed line refers to the variable length of the +strand.

Both C and P (green and blue, respectively) are translated from the largest (3.5kb) mRNA.  Approximately 200 copies of C are produced for each copy of P.

The Pre-C and C protein are made from mRNAs that start at the same promoter.  One mRNA (3.5kb) is slightly longer and is translated to pre-C.  Another mRNA (3.5kb) is slightly shorter than pre-C RNA, because it lacks the AUG used to initiate translation of pre-C.  A downstream AUG in this mRNA is used to initiate the translation (still within frame) of C protein, the major capsid protein of the virion.  Pre-C is inserted into the ER during synthesis and transported through secretory vesicles, undergoing cleavage of N-terminal signal sequence and C-terminal residues.  Pre-C is then secreted from the cell as a 17-kDa protein called HBeAg. HBeAg is believed to be important in establishing chronic infection infants and more aggressive clinical hepatitis.

The gene for P protein is downstream of C.  It partially overlaps with C and is in a different reading frame. P is translated from the same mRNA as C (3.5kb) but initiation is internal, using a start AUG rather than being produced by some form of frame shifting or cleavage.  Internal initiation is not thought to be associated with an IRES, as in picornaviruses, but it is known to be cap-dependent. The P gene takes up three-fourths of the genome and overlaps with the other three proteins.

Three copies of S are produced (pre-S1, pre-S2, and S).  They are produced using different in-frame AUG initiation codons, but they all have the same N-terminus ending.  PreS1 is translated from the 2.4 kb mRNA, while preS2 and S are translated from two forms of the 2.1 kb mRNA in a manner similar to pre-C and C. Pre-S1 is the longest, pre-S2 is of middle length, and S protein is the smallest. The S protein is completely contained within the P gene as indicated in diagram above.

X is translated from the 0.7-kb mRNA.