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Infection of Cells by Varicella Zoster Virus: Inhibition of Viral Entry by Mannose 6-Phosphate and Heparin
Zhenglun Zhu, Michael D. Gershon, Richard Ambron, Christopher Gabel and Anne A. Gershon
Proceedings of the National Academy of Sciences of the United States of America
Vol. 92, No. 8 (Apr. 11, 1995), pp. 3546-3550
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2367104
Page Count: 5
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Envelope glycoproteins of varicella zoster virus (VZV) contain mannose 6-phosphate (Man6P) residues. We now report that Man6P competitively and selectively inhibits infection of cells in vitro by cell-free VZV; furthermore, dephosphorylation of VZV by exposure to alkaline phosphatase rapidly destroys infectivity. Cells are also protected from VZV in a concentration-dependent manner by heparin (ED50 = 0.23 μg/ml; 95% confidence limits = 0.16-0.26 μ/ml) but not by chondroitin sulfate. Both heparin and Man6P are protective only when present about the time of inoculation. Heparin but not Man6P interferes with the attachment of VZV to cell surfaces; moreover, VZV binds to heparin-affinity columns. These data are compatible with a working hypothesis, whereby VZV attaches to cell surfaces by binding to a heparan sulfate proteoglycan. This binding stabilizes VZV, making possible a low-affinity interaction with another Man6P-dependent receptor, which is necessary for viral entry.
Proceedings of the National Academy of Sciences of the United States of America © 1995 National Academy of Sciences