Human herpesvirus 8 interaction with target cells involves heparan sulfate

Human herpesvirus 8 (HHV-8) or Kaposi's sarcoma associated herpesvirus (KSH V) is associated with Kaposi's sarcoma and primary effusion lymphoma. In vi vo, HHV-8 DNA and transcripts have been detected in B cells, endothelial ce lls, macrophages, and epithelial cells. HHV-8 infects a variety of cell lin es of human and animal origin, leading to latent or abortive infection. Thi s study shows that the broad cellular tropism of HHV-8 may be in part due t o its interaction with the ubiquitous host cell surface molecule, heparan s ulfate (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 MS. Chondroitin sulfates A and C did not inhibit HHV-8 infection, (ii) Enz ymatic removal of HFF cell surface HS with heparinase I and III reduced HHV -8 infection. (iii) Soluble heparin inhibited the binding of radiolabeled H HV-8 to human B cell lines, embryonic kidney epithelial (293) cells, and HF F cells, suggesting interference at tile virus attachment stage. (iv) Cell surface adsorbed HHV-8 was displaced by soluble heparin. (v) Radiolabeled H HV-8 also bound to wild-type MS expressing Chinese hamster ovary (CHO-K1) c ells. 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 t o cells by binding to cell surface MS-like moieties. Heparin did not comple tely prevent the binding and infectivity of HHV-8, suggesting that HHV-8 in teractions with HS could be the first set of ligand-receptor interaction le ading to the binding with one or more host cell receptors essential for the subsequent viral entry process. (C) 2001 Academic Press.