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Science 320 (5875): 531-535

Copyright © 2008 by the American Association for the Advancement of Science

Vaccinia Virus Uses Macropinocytosis and Apoptotic Mimicry to Enter Host Cells

Jason Mercer, and Ari Helenius*

Abstract: Viruses employ many different strategies to enter host cells. Vaccinia virus, a prototype poxvirus, enters cells in a pH-dependent fashion. Live cell imaging showed that fluorescent virus particles associated with and moved along filopodia to the cell body, where they were internalized after inducing the extrusion of large transient membrane blebs. p21-activated kinase 1 (PAK1) was activated by the virus, and the endocytic process had the general characteristics of macropinocytosis. The induction of blebs, the endocytic event, and infection were all critically dependent on the presence of exposed phosphatidylserine in the viral membrane, which suggests that vaccinia virus uses apoptotic mimicry to enter cells.

ETH Zurich, Institute of Biochemistry, Schafmattstrasse 18, ETH Hönggerberg HPM E6.3 Zurich, Switzerland.

* To whom correspondence should be addressed. E-mail: ari.helenius{at}

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