Organization of the X gene region of the hepatitis B virus genome

Abstract

In the hepatitis B virus (HBV) genome four long open reading frames (ORFs) have been found that encode the virus core, surface and polymerase proteins as well as a protein that appears to be involved in virus gene expression (X). However, all HBV genomes examined contain two addition ORFs designated ORF5 and ORF6. ORF5 is located on the same strand as the four known viral genes and is 70-100 codons in size. ORF6 is located on the DNA strand complementary to the one that encodes the other virus genes, and is approximately 210 codons in length. Both ORFs are located in the X gene region which corresponds to the 3' terminus of the linear RNA genome. Northern blot analysis identified an X region specific transcript of approximately 0.7 kb. Although this transcript may be the template for the translation of the X gene protein it may also be involved in the expression of the protein encoded by ORF5. The promoter for this transcript may consist, in part, of the 15 residue sequence GCYTGYYTTGCYCGC because this sequence is near the 5' end of the transcript, it is highly conserved among hepadnaviruses, and it contains sequences involved in RNA polymerase binding. Also, the nucleotides within this region of the hepadnavirus genome are capable of forming a stable (G = -18 kcal/mole) hairpin structure. Understanding the organization and gene expression of the X region may be crucial in expanding our knowledge on the biology of HBV.