Cell surface heparan sulfate is a receptor for human herpesvirus 8 and interacts with envelope glycoprotein K8.1

An immunodominant envelope glycoprotein is encoded by the human herpesvirus 8 (HHV-8) (also termed Kaposi's sarcoma-associated herpesvirus) K8.1 gene. The functional role of glycoprotein K8.1 is unknown, and recognizable sequ ence homology to K8.1 is not detectable in the genomes of most other closel y related gamma-herpesviruses, such as herpesvirus saimiri or Epstein-Barr virus. In search for a possible function for K8.1, we expressed the ectodom ain of K8.1 fused to the Fc part of human immunoglobulin G1 (K8.1 Delta TMF c). K8.1 Delta TMFc specifically bound to the surface of cells expressing g lycosaminoglycans but not to mutant cell lines negative for the expression of heparan sulfate proteoglycans. Binding of K8.1 Delta TMFc to mammalian c ells could be blocked by heparin. Interestingly, the infection of primary h uman endothelial cells by HHV-8 could also be blocked by similar concentrat ions of heparin. The specificity and affinity of these interactions were th en determined by surface plasmon resonance measurements using immobilized h eparin and soluble K8.1. This revealed that K8.1 binds to heparin with an a ffinity comparable to that of glycoproteins B and C of herpes simplex virus , which are known to be involved in target cell recognition by binding to c ell surface proteoglycans, especially heparan sulfate. We conclude that cel l surface glycosaminoglycans play a crucial role in HHV-8 target cell recog nition and that HHV-8 envelope protein K8.1 is at least one of the proteins involved.