Human herpesvirus 8 interaction with target cells involves heparan sulfate.

Abstract

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.

• Authors: S M Akula, F Z Wang, J Vieira, B Chandran
• Journal: Virology (Virology) Vol. 282 Issue 2 Pg. 245-55 (Apr 10 2001) ISSN: 0042-6822 [Print] United States
• PMID: 11289807 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Receptors, Virus
• Heparin
• Chondroitin Sulfates
• Heparitin Sulfate
• Heparin Lyase

Topics

• Adsorption (drug effects)
• Animals
• B-Lymphocytes (drug effects, metabolism, ultrastructure, virology)
• Cell Line
• Chondroitin Sulfates (pharmacology)
• Cricetinae
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, metabolism, virology)
• Fibroblasts (drug effects, metabolism, virology)
• Heparin (pharmacology)
• Heparin Lyase (metabolism)
• Heparitin Sulfate (antagonists & inhibitors, deficiency, genetics, metabolism)
• Herpesvirus 8, Human (drug effects, metabolism, ultrastructure)
• Humans
• Microscopy, Electron
• Mutation
• Receptors, Virus (antagonists & inhibitors, deficiency, genetics, metabolism)
• Solubility