Sulphated and sulphonated polymers inhibit the initial interaction of hepatitis B virus with hepatocytes.
The initial step during hepatitis B virus (HBV) infection is the specific attachment of the virus to the hepatocyte. Here we studied whether the binding of HBV to hepatocytes can, as is the case with most other enveloped viruses, be blocked by polyanionic compounds. Viral particles produced by HepAD38 cells were used as inoculum and HBV-negative HepG2 cells, as well as primary human hepatocytes, as target cells. Three sulphated polymers, that is, PAVAS (a co-polymer of acrylic acid with vinyl alcohol sulphate), heparin and dextran sulphate (DS) (MW 5000), and the sulphonated polymer PAMPS [poly(2-acryl-amido-2-methyl-1-propanesulfonic acid] (MW approximately 7000-12000), proved strong inhibitors of the binding of HBV to HepG2 cells and primary hepatocytes. The 50% effective concentration (EC50) for inhibition of HBV binding to HepG2 cells by PAVAS, heparin, DS and PAMPS was 1.3 microg/ml, 1.6 microg/ml, 1.8 microg/ml and 3.3 microg/ml, respectively, and to primary hepatocytes 1.6 microg/ml (PAVAS), 1.6 microg/ml (heparin), 2.6 microg/ml (DS) and 4.1 microg/ml (PAMPS). These values are in the same range as the concentrations required for these compounds to prevent such viruses as herpesviruses and HIV from binding to cells. These findings may be helpful in elucidating the mechanism of the initial interaction of HBV with hepatocytes.
Ying
C
C
Rega Institute for Medical Research, Laboratory of Virology, KU Leuven, Belgium.
Van Pelt
J F
JF
Van Lommel
A
A
Van Ranst
M
M
Leyssen
P
P
De Clercq
E
E
Neyts
J
J
D000180:Acrylic Resins / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D016264:Dextran Sulfate / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D019763:Heparin Lyase / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects* / Q000821:virology*; D006801:Humans; D016015:Logistic Models; D008565:Membrane Proteins / Q000378:metabolism; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology
D000180:Acrylic Resins; D000998:Antiviral Agents; D008565:Membrane Proteins; D011108:Polymers; D013451:Sulfonic Acids; C063252:sulfated acrylic acid-vinyl alcohol copolymer; C077118:poly(2-acrylamido-2-methyl-1-propanesulfonic acid); D006493:Heparin; D016264:Dextran Sulfate; D019763:Heparin Lyase