BIOPHYSICAL THEORY AND MODELING |
The stochastic entry of enveloped viruses: Fusion vs.
endocytosis
Tom Chou 1*
1 UCLA
* To whom correspondence should be addressed. E-mail: tomchou{at}ucla.edu.
Submitted on February 14, 2007
Revised on March 19, 2007
Accepted on 13 April 2007
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Abstract |
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Infection by membrane-enveloped viruses requires the binding of receptors on the target cell membrane to glycoproteins, or "spikes," on the viral membrane. The initial entry is usually classified as fusogenic or endocytotic. However, binding of viral spikes to cell surface receptors not only initiates the viral adhesion and the wrapping process necessary for internalization, but can simultaneously initiate direct fusion with the cell membrane. Both fusion and internalization have been observed to be viable pathways for many viruses. We develop a stochastic model for viral entry that incorporates a competition between receptor mediated fusion and endocytosis. The relative probabilities of fusion and endocytosis of a virus particle initially nonspecifically adsorbed on the host cell membrane are computed as functions of receptor concentration, binding strength, and number of spikes. We find different parameter regimes where the entry pathway probabilities can be analytically expressed. Experimental tests of our mechanistic hypotheses are proposed and discussed.
Key Words:
endocytosis, fusion, stochastic, viral entry
