Attachment sites and neutralising epitopes of hepatitis B virus.
Hepatitis B virus (HBV), the prototype of the family Hepadnaviridae is an organ and species-specific human pathogen. Although our knowledge about the molecular biology of this highly liver-specific virus has increased, the mechanism of attachment and entry into its host cell, the differentiated hepatocytes is still enigmatic. Numerous potential cellular binding sites for the 3 HBV-surface proteins have been described in the past, but none of them have been proven to be a functional receptor. The difficulty in studying attachment and entry of HBV was mainly due to the lack of an easily accessible in vitro infection system. For over 20 years, primary human hepatocytes from surgically excised liver specimens were the only in vitro model, while the available hepatoma cell lines were not susceptible to HBV. Surprisingly, primary hepatocyte cultures from Tupaias (tree shrews) turned out to be susceptible for HBV. Using Tupaia hepatocytes we were able to determine the neutralising capacity of monoclonal and polyclonal antibodies against HBV. Mapping of the neutralising epitopes and inhibition of infection by competing preS1 lipopeptides enabled us and others to identify amino acids 9-18 of the preS1 domain as conserved minimal attachment site and amino acids 28-48 as accessory binding sites. Based on these data it should be possible to identify the cellular receptors for this attachment site. Furthermore we could distinguish between preS1-dependent attachment and subsequent S domain-dependent steps in the infection process. Not all S-binding antibodies are able to neutralize the infectivity. This should be considered when the protective efficacy of HBV vaccine induced antibodies is determined.
Glebe
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Institute of Medical Virology, Justus-Liebig University Giessen, Frankfurter Strasse 107, D-35392 Giessen, Germany. dieter.glebe@viro.med.uni-giessen.de
D000939:Epitopes / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology* / Q000472:pathogenicity; D011498:Protein Precursors / Q000276:immunology; D011991:Receptors, Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C050806:presurface protein 1, hepatitis B surface antigen