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Journal of Virology, December 2001, p. 11583-11593, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11583-11593.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cell Surface Heparan Sulfate Is a Receptor for Human Herpesvirus 8 and Interacts with Envelope Glycoprotein K8.1

Alexander Birkmann,1 Kerstin Mahr,2 Armin Ensser,1 Svenja Yaguboglu,1 Fritz Titgemeyer,2 Bernhard Fleckenstein,1 and Frank Neipel1,*

Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, D-91054 Erlangen,1 and Lehrstuhl für Mikrobiologie, Institut für Mikrobiologie, Biochemie und Genetik, Universität Erlangen-Nürnberg, D-91058 Erlangen,2 Germany

Received 15 March 2001/Accepted 24 August 2001

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 sequence homology to K8.1 is not detectable in the genomes of most other closely related gammaherpesviruses, such as herpesvirus saimiri or Epstein-Barr virus. In search for a possible function for K8.1, we expressed the ectodomain of K8.1 fused to the Fc part of human immunoglobulin G1 (K8.1Delta TMFc). K8.1Delta TMFc specifically bound to the surface of cells expressing glycosaminoglycans but not to mutant cell lines negative for the expression of heparan sulfate proteoglycans. Binding of K8.1Delta TMFc to mammalian cells could be blocked by heparin. Interestingly, the infection of primary human endothelial cells by HHV-8 could also be blocked by similar concentrations of heparin. The specificity and affinity of these interactions were then determined by surface plasmon resonance measurements using immobilized heparin and soluble K8.1. This revealed that K8.1 binds to heparin with an affinity 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 cell surface proteoglycans, especially heparan sulfate. We conclude that cell surface glycosaminoglycans play a crucial role in HHV-8 target cell recognition and that HHV-8 envelope protein K8.1 is at least one of the proteins involved.

* Corresponding author. Mailing address: Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany. Phone: (49)-9131-8526483. Fax: (49)-9131-8526599. E-mail: neipel{at}viro.med.uni-erlangen.de.

Journal of Virology, December 2001, p. 11583-11593, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11583-11593.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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