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.
ubo
lu,1Institut 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
(K8.1
TMFc). K8.1
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 K8.1
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.
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