ACTIVATION OF THE ENVELOPE PROTEINS BY A METALLOPROTEINASE ENABLES ATTACHMENT AND ENTRY OF THE HEPATITIS-B VIRUS INTO T-LYMPHOCYTE

Previously, we identified an HBV binding factor (HBV-BF), a 50-kDa ser um glycoprotein which interacts with HBV envelope proteins and which i s also located in the membrane of normal human hepatocyte (A. Budkowsk a et al. (1993) J. Virol. 67, 4316), Here we show that HBV-BF is a neu tral metalloproteinase which shares substrate specificity and properti es with a newly described family of membrane type matrix metalloprotei nases. HBV-BF treatment of the HBV resulted in the cleavage of the N-t erminal part of the middle HBV envelope protein at the pre-S2(136-141) amino acid sequence VRGLYF/L (containing a single arginine cleavage s ite). HBV-BF affected the reactivity of the large HBV protein with pre -S1-specific MAbs, probably inducing the conformational change of the pre-S1 domain. The HBV-BF-digested virus remained morphologically inta ct with unchanged S antigenic determinants. The structural modificatio ns of the Viral envelope proteins induced by HBV-BF enabled cell membr ane attachment and viral entry into the T-lymphocyte. Both processes w ere blocked by the metalloproteinase inhibitor 1,10 phenanthroline. Th us, the host-dependent proteolytic activation of the envelope proteins seems to be essential for the HBV entry into the cell. HBV-BF under a membrane bound or a secreted form could be (one of) the molecule(s) r esponsible for the HBV proteolytic activation. (C) 1997 Academic Press .