Pre-s1 antigen-dependent infection of Tupaia hepatocyte cultures with human hepatitis B virus.
The susceptibility of the tree shrew Tupaia belangeri to human hepatitis B virus (HBV) has been demonstrated both in vivo and in vitro. In this study, we show that purified HBV infects primary T. belangeri hepatocyte cultures in a very specific manner, as detected by HBV covalently closed circular DNA, mRNA, HBV e antigen, and HBsAg production. A monoclonal antibody (MAb), MA18/7, directed against the pre-S1 domain of the large HBs protein, which has been shown to neutralize infectivity of HBV for primary human hepatocytes, also blocked infection of primary Tupaia hepatocytes. MAbs against the pre-S2 domain of HBs inhibited infection only partially, whereas an S MAb and polyvalent anti-HBs antibodies neutralized infection completely. Thus, both pre-S1 and S antigens are necessary for infection in the tupaia. Using subviral particles, >70% of primary Tupaia hepatocytes are capable of specific binding of pre-S1-rich HBsAg, showing localization in distinct membrane areas. The data show that the early steps of HBV infection in Tupaia hepatocyte cultures are comparable to those in the human system.
Glebe
Dieter
D
Institute of Medical Virology. Institute of Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany. dieter.glebe@viro.med.unigiessen.de
Aliakbari
Mehriar
M
Krass
Peter
P
Knoop
Eva V
EV
Valerius
Klaus P
KP
Gerlich
Wolfram H
WH
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000502:physiology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D007700:Kinetics; D009500:Neutralization Tests; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology*; D014417:Tupaia; D014779:Virus Replication
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen