Studies on the attachment and penetration of hepatitis B virus

There are two identified liver-specific attachment sites in the preS2 domain and one in the preS1 domain. Which mechanism leads to attachment in vivo is not known. The subsequent penetration seems to require proteolysis which does not occur spontaneously in HepG2 cells, but presumably in vivo. The role of the small HBs protein for attachment remains enigmatic so far, but it must have a function because an escape mutant exists against a monoclonal antibody which binds to an epitope of the small protein. The occurrence of this escape mutant in vaccinated persons proves that the standard hepatitis B vaccine does induce neutralizing antibodies, but it also suggests very strongly that the neutralizing preS epitopes be included in future hepatitis B vaccines.