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 B cells, endothelial cells, macrophages, and epithelial cells. HHV-8 infects a variety of human and animal cell lines leading to latent or abortive infection. Our studies showed that this broad cellular tropism may be in part due to HHV-8's interaction with the ubiquitous host cell-surface HS-like molecules. HHV-8 binding to the target cells and the infection were inhibited by soluble heparan, a glycosaminoglycan (GAG) closely related to HS. Since HHV-8 gB possess a putative heparan-binding domain (HBD) in the extracellular domain, the interaction of gB with HS-like moieties was examined. Unlike gB of gamma1-Epstein-Barr virus and gamma2-murine herpesvirus 68, HHV-8 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 antibodies neutralized HHV-8 infection. Virion envelope-associated gB specifically bound to heparan-agarose, which was eluted by high concentration of soluble heparan, but not by chondroitin sulfates. In vitro transcribed and translated products of gB gene specifically bound to heparan-agarose beads, which 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. Biotinylated gB peptide corresponding to the putative HBD also bound to heparan. These results suggest that gB plays an important role in the infectious process of HHV-8 and virus interaction with cell-surface HS-like moieties could be in part mediated by the envelope-associated gB.
Akula
S M
SM
Department of Microbiology, Molecular Genetics and Immunology, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Pramod
N P
NP
Wang
F Z
FZ
Chandran
B
B
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D011991:Receptors, Virus / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*
D000914:Antibodies, Viral; D006023:Glycoproteins; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D010455:Peptides; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C116207:glycoprotein B, human herpesvirus 8