Human herpesvirus 8 interaction with target cells involves heparan sulfate.
Human herpesvirus 8 (HHV-8) or Kaposi's sarcoma associated herpesvirus (KSHV) is associated with Kaposi's sarcoma and primary effusion lymphoma. In vivo, HHV-8 DNA and transcripts have been detected in B cells, endothelial cells, macrophages, and epithelial cells. HHV-8 infects a variety of cell lines of human and animal origin, leading to latent or abortive infection. This study shows that the broad cellular tropism of HHV-8 may be in part due to its interaction with the ubiquitous host cell surface molecule, heparan sulfate (HS). This conclusion is based on the following findings: (i) HHV-8 infection of human foreskin fibroblast (HFF) cells was inhibited in a dose-dependent manner by soluble heparin, a glycosaminoglycan closely related to HS. Chondroitin sulfates A and C did not inhibit HHV-8 infection. (ii) Enzymatic removal of HFF cell surface HS with heparinase I and III reduced HHV-8 infection. (iii) Soluble heparin inhibited the binding of radiolabeled HHV-8 to human B cell lines, embryonic kidney epithelial (293) cells, and HFF cells, suggesting interference at the virus attachment stage. (iv) Cell surface adsorbed HHV-8 was displaced by soluble heparin. (v) Radiolabeled HHV-8 also bound to wild-type HS expressing Chinese hamster ovary (CHO-K1) cells. In contrast, binding of virus to mutant CHO cells deficient in HS was significantly reduced. These data show that the gamma2 herpesvirus HHV-8, similar to some members of alpha, beta, and gamma2 herpesviruses, adsorbs to cells by binding to cell surface HS-like moieties. Heparin did not completely prevent the binding and infectivity of HHV-8, suggesting that HHV-8 interactions with HS could be the first set of ligand-receptor interaction leading to the binding with one or more host cell receptors essential for the subsequent viral entry process.
Akula
S M
SM
Department of Microbiology, Molecular Genetics and Immunology, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Wang
F Z
FZ
Vieira
J
J
Chandran
B
B
D000327:Adsorption / Q000187:drug effects; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D006493:Heparin / Q000494:pharmacology; D019763:Heparin Lyase / Q000378:metabolism; D006497:Heparan Sulfate / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D009154:Mutation; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012995:Solubility
D002809:Chondroitin Sulfates; D006493:Heparin; D019763:Heparin Lyase; D006497:Heparan Sulfate; D011991:Receptors, Virus