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Vaccinia extracellular virions enter cells by macropinocytosis and acid-activated membrane rupture.


ABSTRACT: Vaccinia virus (VACV), the model poxvirus, produces two types of infectious particles: mature virions (MVs) and extracellular virions (EVs). EV particles possess two membranes and therefore require an unusual cellular entry mechanism. By a combination of fluorescence and electron microscopy as well as flow cytometry, we investigated the cellular processes that EVs required to infect HeLa cells. We found that EV particles were endocytosed, and that internalization and infection depended on actin rearrangements, activity of Na(+)/H(+) exchangers, and signalling events typical for the macropinocytic mechanism of endocytosis. To promote their internalization, EVs were capable of actively triggering macropinocytosis. EV infection also required vacuolar acidification, and acid exposure in endocytic vacuoles was needed to disrupt the outer EV membrane. Once exposed, the underlying MV-like particle presumably fused its single membrane with the limiting vacuolar membrane. Release of the viral core into the host cell cytosol allowed for productive infection.

SUBMITTER: Schmidt FI 

PROVIDER: S-EPMC3181475 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Vaccinia extracellular virions enter cells by macropinocytosis and acid-activated membrane rupture.

Schmidt Florian Ingo FI   Bleck Christopher Karl Ernst CK   Helenius Ari A   Mercer Jason J  

The EMBO journal 20110726 17


Vaccinia virus (VACV), the model poxvirus, produces two types of infectious particles: mature virions (MVs) and extracellular virions (EVs). EV particles possess two membranes and therefore require an unusual cellular entry mechanism. By a combination of fluorescence and electron microscopy as well as flow cytometry, we investigated the cellular processes that EVs required to infect HeLa cells. We found that EV particles were endocytosed, and that internalization and infection depended on actin  ...[more]

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