A range of proteins has been recognized as mediators/hypothetical receptors for hepatitis B virus (HBV), but the results are conflicting and inconclusive especially regarding their biological significance. This study was aimed at identifying a novel HBV-interacting protein which would provide a better understanding of its transport in blood, attachment, fusion and entry into hepatocytes. Serum samples positive for HBV confirmed by PCR were subjected to ammonium sulfate fractionations at 50, 75, 100%, saturation. PCR of each fraction demonstrated amplification of HBV in 100% fraction. Protein analysis by SDS PAGE of fractions showed one band of approximately 69 kDa protein, in 100% fraction. The 100% fraction band was excised from gel and sequence was determined by MALDI TOF which showed mass values from 705 to 3722. Mass spectrometry of trypsinized 69 kDa species revealed peptide sequences that covered 54% of the serum albumin precursor amino acid sequence, with pI of 5.9. Western blot, carried out using primary anti-albumin precursor antibody, further validated this protein. This study establishes that Hepatitis B Virus binds to albumin precursor, suggesting its role in the initiation of HBV infection and hence may offer new therapeutic strategies against HBV infection
