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JVI Accepts, published online ahead of print on 5 September 2007
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J. Virol. doi:10.1128/JVI.01415-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Affinity thresholds for membrane fusion triggering by viral glycoproteins

Kosei Hasegawa, Chunling Hu, Takafumi Nakamura, James D Marks, Stephen J Russell, and Kah-Whye Peng*

Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Anesthesia, University of California San Francisco, San Francisco, CA 94110, USA

* To whom correspondence should be addressed. Email: peng.kah{at}mayo.edu.


   Abstract

Enveloped viruses trigger membrane fusion to gain entry into cells. The receptor affinities of their attachment proteins vary greatly, from 10-4 M to 10-9 M, but the significance of this is unknown. Using six retargeted measles viruses that bind to Her-2/neu with a 5-log range in affinity, we show that receptor affinity has little impact on virus attachment but is nevertheless a key determinant of infectivity and intercellular fusion. For a given cell surface receptor density, there is an affinity threshold above which cell-cell fusion proceeds efficiently. Suprathreshold affinities do not further enhance the efficiency of membrane fusion.







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