Hepatitis B virus surface antigen binds to apolipoprotein H.
We have previously demonstrated that a plasma membrane-enriched fraction isolated from human liver is capable of binding recombinant hepatitis B surface antigen (rHBsAg) (P. Pontisso, M. A. Petit, M. Bankowski, and M. E. Peeples, J. Virol. 63:1981-1988, 1989). In this study we have separated the plasma membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and used a ligand-blotting technique to identify a 46-kDa rHBsAg-binding protein. This protein could be removed from the membranes with a weakly acidic buffer, implying that it is peripherally bound. Examination of human serum revealed that the 46-kDa binding protein is a serum protein. Isolation of plasma lipoproteins revealed that the binding protein is in part associated with chylomicrons and high-density lipoproteins, both of which are targeted to the hepatocyte during the normal course of lipid metabolism. The binding protein was identified as apolipoprotein H (apo H), also known as beta 2-glycoprotein I, on the basis of copurification of the rHBsAg-binding activity with the apo H protein and the ability of cDNA-expressed apo H to bind rHBsAg. Serum-derived HBsAg also binds to apo H, indicating that binding is not unique to rHBsAg. Binding is saturable, requires only the small S protein of rHBsAg, and is inhibited by excess rHBsAg, antibodies to HBsAg, and antibodies to apo H. The binding activity of apo H is destroyed upon reduction, indicating that 1 or more of its 22 disulfide bonds are required for interaction with rHBsAg. The possibility that an interaction between hepatitis B virus particles and lipoprotein particles may facilitate entry of the virus into hepatocytes is discussed.
Mehdi
H
H
Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3864.
Kaplan
M J
MJ
Anlar
F Y
FY
Yang
X
X
Bayer
R
R
Sutherland
K
K
Peeples
M E
ME
D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D053482:beta 2-Glycoprotein I
D001053:Apolipoproteins; D006023:Glycoproteins; D006514:Hepatitis B Surface Antigens; D008565:Membrane Proteins; D011994:Recombinant Proteins; D053482:beta 2-Glycoprotein I