title: Purinergic receptor functionality is necessary for infection of human hepatocytes by hepatitis delta virus and hepatitis B virus.
abstract: Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are major sources of acute and chronic hepatitis. HDV requires the envelope proteins of HBV for the processes of assembly and infection of new cells. Both viruses are able to infect hepatocytes though previous studies have failed to determine the mechanism of entry into such cells. This study began with evidence that suramin, a symmetrical hexasulfated napthylurea, could block HDV entry into primary human hepatocytes (PHH) and was then extrapolated to incorporate findings of others that suramin is one of many compounds that can block activation of purinergic receptors. Thus other inhibitors, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS) and brilliant blue G (BBG), both structurally unrelated to suramin, were tested and found to inhibit HDV and HBV infections of PHH. BBG, unlike suramin and PPADS, is known to be more specific for just one purinergic receptor, P2X7. These studies provide the first evidence that purinergic receptor functionality is necessary for virus entry. Furthermore, since P2X7 activation is known to be a major component of inflammatory responses, it is proposed that HDV and HBV attachment to susceptible cells, might also contribute to inflammation in the liver, that is, hepatitis.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America. john.taylor@fccc.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Taylor
authors.forename: Ziying
authors.initials: Z
authors.lastname: Han
mesh_terms: D000818:Animals; D002460:Cell Line; D006515:Hepatitis B virus / Q000378:metabolism*; D003698:Hepatitis Delta Virus / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007249:Inflammation; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D012367:RNA, Viral / Q000378:metabolism; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D012394:Rosaniline Dyes / Q000494:pharmacology; D013498:Suramin / Q000737:chemistry
chemical_list: D012367:RNA, Viral; D011983:Receptors, Purinergic; D058486:Receptors, Purinergic P2X7; D012394:Rosaniline Dyes; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; C004692:coomassie Brilliant Blue