Human herpesvirus 8 envelope-associated glycoprotein B interacts with heparan sulfate-like moieties

Cell-surface heparan sulfate (HS) serves as an initial attachment receptor for several herpesviruses. The gamma2-human herpesvirus-8 (HHV-8) or Kaposi 's sarcoma associated herpesvirus DNA and transcripts have been detected in a cells, endothelial cells, macrophages, and epithelial cells. HHV-8 infec ts a variety of human and animal cell lines leading to latent or abortive i nfection. Our studies showed that this broad cellular tropism may be in par t due to HHV-8's interaction with the ubiquitous host cell-surface MS-like molecules. HHV-B binding to the target cells and the infection were inhibit ed by soluble heparan, a glycosaminoglycan (GAG) closely related to HS. Sin ce HHV-8 gB possess a putative heparan-binding domain (HBD) in the extracel lular domain, the interaction of gB with MS-like moieties was examined. Unl ike gB of gammal-Epstein-Barr virus and gamma2-murine herpesvirus 68, HHV-B gB was expressed on the surface of the infected cell membranes and virion envelopes. Envelope-associated gB was made up of 75 and 54 kDa polypeptides forming disulfide-linked heterodimers and multimers. Rabbit anti-gB antibo dies neutralized HHV-8 infection. Virion envelope-associated gB specificall y bound to heparan-agarose, which was eluted by high concentration of solub le heparan, but not by chondroitin sulfates. In vitro transcribed and trans lated products of gB gene specifically bound to heparan-aga rose beads, whi ch was blocked by HS and heparan, but not by other GAGs such as chondroitin sulfates (A, B, and C), N-acetyl heparan, and de-N-sulfated heparan. Bioti nylated gB peptide corresponding to the putative HBD also bound to heparan. These results suggest that gB plays an important role in the infectious pr ocess of HHV-B and virus interaction with cell-surface MS-like moieties cou ld be in part mediated by the envelope-associated gB. (C) 2001 Academic Pre ss.