Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues

J Virol. 2007 Jun;81(11):5841-9. doi: 10.1128/JVI.00096-07. Epub 2007 Mar 21.


The N-terminal pre-S domain of the large hepatitis B virus (HBV) envelope protein plays a pivotal role at the initial step of the viral entry pathway. In the present study, the entire pre-S domain was mapped for infectivity determinants, following a reverse-genetics approach and using in vitro infection assays with hepatitis delta virus (HDV) or HBV particles. The results demonstrate that lesions created within the N-terminal 75 amino acids of the pre-S region abrogate infectivity, whereas mutations between amino acids 76 and 113, overlapping the matrix domain, had no effect. In contrast to the results of a recent study (L. Stoeckl, A. Funk, A. Kopitzki, B. Brandenburg, S. Oess, H. Will, H. Sirma, and E. Hildt, Proc. Natl. Acad. Sci. 103:6730-6734, 2006), the deletion of a cell membrane translocation motif (TLM) located between amino acids 148 and 161 at the C terminus of pre-S2 did not interfere with the infectivity of the resulting HDV or HBV mutants. Furthermore, a series of large deletions overlapping the pre-S2 domain were compatible with infectivity, although the efficiency of infection was reduced when the deletions extended to the pre-S1 domain. Overall, the results demonstrate that the activity of the pre-S domain at viral entry solely depends on the integrity of its first 75 amino acids and thus excludes any function of the matrix domain or TLM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Amino Acid Sequence
  • Amino Acids / chemistry*
  • Amino Acids / genetics
  • Amino Acids / physiology*
  • Cell Line, Tumor
  • Hepatitis B / metabolism
  • Hepatitis B / virology
  • Hepatitis B Surface Antigens / chemistry*
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / physiology*
  • Hepatitis B virus / chemistry*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / pathogenicity*
  • Hepatitis Delta Virus / chemistry
  • Hepatitis Delta Virus / genetics
  • Hepatitis Delta Virus / pathogenicity
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / physiology
  • Protein Precursors / chemistry*
  • Protein Precursors / genetics
  • Protein Precursors / physiology*
  • Protein Structure, Tertiary / genetics
  • Protein Transport / genetics
  • Sequence Deletion / genetics
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / physiology


  • Amino Acids
  • Hepatitis B Surface Antigens
  • L protein, hepatitis B virus
  • Peptide Fragments
  • Protein Precursors
  • Viral Envelope Proteins
  • presurface protein 1, hepatitis B surface antigen
  • presurface protein 2, hepatitis B surface antigen