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Journal of Virology, December 2007, p. 13149-13157, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01415-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Affinity Thresholds for Membrane Fusion Triggering by Viral Glycoproteins{triangledown}

Kosei Hasegawa,1 Chunling Hu,1 Takafumi Nakamura,1,{dagger} James D. Marks,2 Stephen J. Russell,1 and Kah-Whye Peng1*

Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905,1 Department of Anesthesia, University of California San Francisco, San Francisco, California 941102

Received 28 June 2007/ Accepted 29 August 2007

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 viral 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.

* Corresponding author. Mailing address: Molecular Medicine Program, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905. Phone: (507) 284-8357. Fax: (507) 284-8388. E-mail: peng.kah{at}mayo.edu

{triangledown} Published ahead of print on 5 September 2007.

{dagger} Present address: Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.

Journal of Virology, December 2007, p. 13149-13157, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01415-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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