Hepatitis B Virus Dane Particles Bind to Human Plasma Apolipoprotein H

Abstract

Human apolipoprotein H (apo H)The hepatitis B virus (HBV) chronically infects more than 250 million people throughout the world, and is the most important etiologic agent responsible for diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma in endemic areas. 1 This DNA virus is a member of the Hepadnaviridae family 2 and mainly targets liver cells. The HBV envelope contains the hepatitis B surface antigen (HBsAg), which is a complex macromolecular aggregate with an M r of 3.5 ϫ 10 6 composed of proteins (75%), carbohydrates in glycoprotein form, and lipids from the host (25%). 3 HBsAg occurs in three molecular forms, named small (S), middle (M), and large (L) HBsAg. The SHBsAg contains 226 amino acid residues and the MHBsAg has an additional pre-S2 domain (55 amino acid residues), whereas the LHBsAg has the pre-S2 and pre-S1 extension (119 amino acid residues). During HBV infection, hepatocytes synthesize and secrete HBsAg mainly in the form of 20-nm diameter lipoproteic particles. 4 Phospholipids represent almost 70% of total lipids, with phosphatidylcholine being the most abundant component. 5 Two other types of virus-associated particles are present in the blood of HBV-infected subjects: Dane spherical particles with a diameter of about 42 nm, consisting of infectious complete virions and smaller quantities of filaments of variable length. The 20-nm HBsAg spheres are usually present in a 10,000-to 1,000,000-fold excess over Dane particles. 6 A variety of serum-derived proteins binds to HBV envelope glycoproteins. Altered human serum albumin, especially glutaraldehyde polymerized albumin (poly-HSA), has been the most studied. 7,8 The HBsAg receptor for poly-HSA has been localized within the pre-S2 domain, 9 and is more abundant in the hepatitis B e antigen (HBeAg) phase of HBV infection than in the anti-HBe phase. 10 A significant correlation was reported between poly-HSA binding activity on HBsAg particles and DNA polymerase, and further this poly-HSA binding activity was proposed as an active infection marker for a prognostic test for HBeAg-positive chronic hepatitis B. 11 This albumin polymers-HBsAg interaction is species specific, and some investigators found that only glutaraldehyde made albumin polymers bind HBsAg efficiently. 12 These controversial results and the fact that the albumin solutions previously used by these investigators were possibly not pure enough, led us to investigate the nature of possible albumin contaminants responsible for this binding activity. We thus purified, from human albumin, a 50-kd protein exhibiting HBsAg binding activity and preventing heat-induced formation of albumin polymers. The first 20 amino acids of the N-terminal region for this protein were determined by gas phase microsequencing: NH 2 -Gly-Arg-Thr-Cys-Pro-Lys-Pro-Asp-Asp-Leu-ProPhe-Ser-Thr-Val-Val-Pro-Leu-Lys-Thr-. A computer search of current database releases showed that this sequence is identical to the N-terminal sequence of the plasma protein apolipoprotein H (apo H), or ␤2-glycoprote...

Identification and Characterization of Peptides That Interact with Hepatitis B Virus via the Putative Receptor Binding Site

“…More recently, human squamous cell carcinoma antigen 1, a membrane protein, was identified in HepG2 cells and shown to interact with PreS1 (14). In addition, immunoglobulin A receptor (31,34), asialoglycoprotein receptor (43), transferrin receptor (18), apolipoprotein H (28,42), polymerized serum albumin (12,22), annexin V (19), fibronectin (3), and an 50-kDa serum glycoprotein (4) have also been found to interact with HBV, though not via PreS1 . These proteins have no obvious sequence motif in common.…”

Andes Virus Antigens Are Shed in Urine of Patients with Acute Hantavirus Cardiopulmonary Syndrome

“…Several reports show that ApoH also interacts with viral proteins, such as the hepatitis B virus (HBV) antigen and proteins p18, p26, and gp160 of the human immunodeficiency virus (12,30,46,47). Interestingly, studies involving binding to the HBV antigen suggest that ApoH specifically binds DNAcontaining HBV particles, thus discriminating, through an undefined mechanism, between active replicating virus and empty noninfectious particles (47).…”

Transactivating effect of complete S protein of hepatitis B virus and cloning of genes transactivated by complete S protein using suppression subtractive hybridization technique

“…It is the pre-S of HBsAg that results in HBsAg combination with APOH. Resecting phosphatide and oxygenated phosphatide could disturb this mutual action, suggesting that this action is involved in the ectoblastic phosphatide [33] . Furthermore, it is restrained from rebuilding HBsAg, anti-HBsAg and APOH.…”

“…APOH may be the vector of HBV and plays a role in HBV infection. APOH chiefly combines with complete Dane HBV particle with telescope, and the activity of APOH-HBsAg is the highest in patients with active duplication [33] . This combination facilitates virus particle entrancing hepatic cells, and plays an important role in the beginning of HBV infection [34] .…”