Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues.
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.
Blanchet
Matthieu
M
Laboratoire de Virologie Moléculaire, Institut National de la Transfusion Sanguine, 6 Rue Alexandre-Cabanel, 75739 Paris, France.
Sureau
Camille
C
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D006509:Hepatitis B / Q000378:metabolism / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006515:Hepatitis B virus / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity*; D003698:Hepatitis Delta Virus / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011498:Protein Precursors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D000596:Amino Acids; D006514:Hepatitis B Surface Antigens; C096362:L protein, hepatitis B virus; D010446:Peptide Fragments; D011498:Protein Precursors; D014759:Viral Envelope Proteins; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen