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 serum glycoprotein which interacts with HBV envelope proteins and which is also located in the membrane of normal human hepatocyte (A. Budkowska et al. (1993) J. Virol. 67, 4316). Here we show that HBV-BF is a neutral metalloproteinase which shares substrate specificity and properties with a newly described family of membrane type matrix metalloproteinases. HBV-BF treatment of the HBV resulted in the cleavage of the N-terminal part of the middle HBV envelope protein at the pre-S2(136-141) amino acid sequence VRGLYF/L (containing a single arginine cleavage site). 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 intact with unchanged S antigenic determinants. The structural modifications of the viral envelope proteins induced by HBV-BF enabled cell membrane attachment and viral entry into the T-lymphocyte. Both processes were blocked by the metalloproteinase inhibitor 1,10 phenanthroline. Thus, 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) responsible for the HBV proteolytic activation.
Budkowska
A
A
Epidémiologie Moléculaire des Entérovirus, Chimie Organique, Station Centrale de Microscopie Electronique, Institut Pasteur, 25 Rue du Dr. Roux, Paris, 75724, USA. abudkow@pasteur.fr
Maillard
P
P
Theret
N
N
Groh
F
F
Possehl
C
C
Topilko
A
A
Crainic
R
R
D000595:Amino Acid Sequence; D002460:Cell Line; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008666:Metalloendopeptidases / Q000502:physiology*; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D013601:T-Lymphocytes / Q000821:virology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
D014759:Viral Envelope Proteins; D008666:Metalloendopeptidases