Fibronectin of human liver sinusoids binds hepatitis B virus: identification by an anti-idiotypic antibody bearing the internal image of the pre-S2 domain

Abstract

Anti-idiotypic antibodies (anti-Ids) have been successfully used to characterize and isolate receptors of several cell ligands. To prepare an immunological probe for identification of cellular components interacting with the hepatitis B virus (HBV), polyclonal antisera against a panel of five HBV-specific monoclonal antibodies (MAbs) were produced in syngeneic BALB/c mice. MAbs to HBV used for immunization (Ab1) recognized biologically important and potentially neutralizing epitopes, located in the pre-S1, pre-S2, or S regionencoded domains of HBV proteins. All the anti-Ids (Ab2) were specific to idiotopes of the homologous Ab1 and inhibited their interaction with the corresponding viral epitopes, suggesting that they recognized unique determinants on the paratope of each immunizing Ab1. Therefore, all five generated polyclonal anti-Ids were of the Ab2 ␤ type and could represent internal images of viral epitopes. Ab2 raised against the pre-S2 region-specific MAb F124 bound to the extracellular matrix fibronectin of human liver sinusoids. Immunohistochemical studies demonstrated the attachment of viral and recombinant (S, M) hepatitis B surface antigen particles with the pre-S2 region-encoded epitopes to the fibronectin of human liver sinusoids. In contrast, recombinant (S, L*) hepatitis B surface antigen particles, in which the epitope recognized by F124 MAb was not expressed, did not show any binding capacity. These findings suggest that human liver fibronectin may bind HBV in vivo by the pre-S2 region-encoded epitopes in a species-restricted manner. Furthermore, binding of the circulating virus to liver sinusoids could facilitate its subsequent uptake by hepatocytes.

Differentially expressed cellular genes following HBV: potential targets of anti‐HBV drugs?

“…Fibronectin is thought to be an important glycoprotein involved in hepatic fibrosis [29]. It had been proposed that this protein may bind HBV in vivo by pre-S2 region-encoded epitopes in a species-restricted manner [30]. The upregulated expression of fibronectin by HBV as demonstrated by our results may show that fibronectin is associated/linked with HBV infection and therefore its level may be positively correlated with the progression of hepatic fibrosis.…”

Interaction of virus populations with their hosts

“…Virus-antibody complex structures show epitopes at receptor recognition sites Tseng et al (2015) Bovine herpesvirus-1 Antiidiotypic antibodies bind to cellular receptors Thaker et al (1994), Varthakavi and Minocha (1996) Human cytomegalovirus Antiidiotypic antibodies bind to cellular receptors Keay et al (1989), Keay and Baldwin (1991) Herpes simplex virus Antiidiotypic antibodies bind to cellular receptors Huang and Campadelli-Fiume (1996) Overlap between a receptor-binding domain in gD and an antigenic site Whitbeck et al (1999) Hepatitis B virus Antiidiotypic antibodies that mimic cellular structures bind to small HBV surface antigen. Synthetic peptide analog is recognized by antiHBV antibodies and cell receptors Neurath et al (1986) Antiidiotypic antibodies bind to cellular receptors Petit et al (1992), Hertogs et al (1994), Budkowska et al (1995) Duck hepatitis B virus Residues involved in the interaction with cells are also critical for virus neutralization Tong et al (1995), Li et al (1996), Sunyach et al (1999 4.5 Trait coevolution: mutual influences between antigenic variation and tropism change…”

Evolution of Cell Recognition by Viruses: A Source of Biological Novelty with Medical Implications

“…Mab recognized epitopes involved in the binding of virions to cellular receptors (Kubo et al, 1993(Kubo et al, , 1994 Flaviviridae BVDV Anti-idiotypic antibodies mimicking viral antigens bind to cellular receptors (Xue and Minocha, 1993;Minocha et al, 1997) Dengue virus Amino acid residues critical for mouse neurovirulence are involved in antibody binding (Hiramatsu et al, 1996) Yellow fever virus Amino acid residues critical for virus neurotropism are involved in antibody binding (Jennings et al, 1994) Hepadnaviridae Duck hepatitis B virus Residues critical for virus neutralization are involved in the interaction with cells (Tong et al, 1995;Li et al, 1996;Sunyach et al, 1999) Hepatitis B virus Anti-idiotypic antibodies mimicking viral antigens bind to cellular receptors (Petit et al, 1992;Hertogs et al, 1994;Budkowska et al, 1995) Anti-idiotypic antibodies mimicking cellular structures bind to small hepatitis B surface antigen (Neurath et al, 1986) A synthetic peptide analogue is recognized by both cell receptors and anti-HBV antibodies (Neurath et al, 1986) Herpesviridae BHV-1 Anti-idiotypic antibodies mimicking viral antigens bind to cellular receptors (Thaker et al, 1994;Varthakavi and Minocha, 1996) HCMV Anti-idiotypic antibodies mimicking viral antigens bind to cellular receptors (Keay et al, 1989;Keay and Baldwin, 1991) HSV Anti-idiotypic antibodies mimicking viral antigens bind to cellular receptors (Huang and Campadelli-Fiume, 1996) Overlap between major neutralizing antigenic site and a receptor-binding domain of gD (Whitbeck et al, 1999) (continues)…”