Deciphering the mystery of hepatitis B virus receptors: A historical perspective

Abstract

Hepatitis B virus is one of the major reasons of viral hepatitis with an estimated 350 million infected patients worldwide. Although, the virus was discovered and cloned more than three decades ago, its entry mechanism has still been in investigation. Numerous potential candidates have been proposed and investigated rigorously to reveal HBV entry mechanism and to unveil the first door of viral entry to hepatocytes. This review provides a short account of role of receptors for entry of HBV into hepatocytes. The viral preS1 region of large surface protein is involved in the attachment of HBV to hepatocytes. The putative attachment site of HBV is located at amino acids 21-47 of preS1. So far, several proteins have been proposed to interact with these different regions of the preS1 domain which includes human immunoglobulin A receptor, glyceraldehyde-3-phosphate dehydrogenase, interleukin-6, a 31-kDa protein, HBV binding factor, asialoglycoprotein receptor, nascent polypeptide-associated complex a polypeptide, lipoprotein lipase, hepatocyteassociated heparan sulfate proteoglycans, glucose-regulated protein 75. However, none of them have appeared to be generally accepted as a true receptor for the virus until recently when sodium taurocholate cotransporting polypeptide identified as HBV entry receptor. Current review provides scientific historical perspective of various candidates known to be interacting with preS1 of HBV for their possible role in viral entry.

Curcumin inhibited hepatitis B viral entry through NTCP binding

“…The L-protein contains preS1 and preS2 sites that bind specifically to host receptors (i.e., NTCP and HSPGs) 2 , 3 . HBV and HDV entered host cells through endocytosis mediated by sodium-taurocholate co-transporting polypeptide (NTCP) and enhanced by heparan sulfate proteoglycans (HSPGs) 4 – 6 . Current HBV treatment includes Pegylated interferon (peg-IFN) and nucleos(t)ide analogs (NAs).…”

Placental expression of asialoglycoprotein receptor associated with Hepatitis B virus transmission from mother to child

“…Hepatitis B virus virions gain entry into hepatocytes via sodium taurocholate cotransporting polypeptide (NTCP) receptor or endocytosis by ASGPR . The ASGPR is a transmembrane molecule specifically expressed on the liver sinusoidal cells, basolateral hepatocellular membrane and dendritic cells, where their key role is not only uptake but also intracellular degradation of desialylated glycoproteins by liver cells .…”

Visualization of hepatitis B virus entry – novel tools and approaches to directly follow virus entry into hepatocytes

“…Over the past 30 years, a number of host factors have been reported to function as putative HBV receptors. They have been identified mostly by binding assays using HBV particles or recombinant envelope proteins . None of these factors have been shown to render nonsusceptible hepatoma cells susceptible to HBV infection.…”