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Published online May 5, 2008
doi:10.1083/jcb.1814rr4
The Journal of Cell Biology, Vol. 181, No. 4, 571-
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Robinson
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Research Roundup

Take a big gulp of pox


Figure 1
A cell exposed to vaccinia (green dots) forms widespread blebs on its surface.

MERCER/AAAS

A poxvirus tricks cells into drinking it up, say Jason Mercer and Ari Helenius (Institute of Biochemistry, Zurich). Vaccinia, studied here, is a prototypical poxvirus, whose members also include the human smallpox virus.

In studying how vaccinia enters cells, the authors observed that mature virus particles bound to filopodia and surfed toward the cell. After arriving at the cell body, the virus particles induced the entire cell surface to erupt into blebs, which, when retracting, engulfed the virus. To the authors' amazement, a single virus particle was sufficient to induce this dramatic behavior.

Entry could be inhibited by the myosin II inhibitor, blebbistatin, as well as by inhibitors of actin dynamics and endosomal fusion. These and other clues, such as the requirement of p21-activated kinase and Na+/H+ exchangers, pointed to a central role for macropinocytosis in viral entry. As confirmation, the authors showed that fluid-phase, but not clathrin-mediated, markers were internalized along with the virus. "This is the first connection of blebbing and macropinocytosis in eukaryotes," says Mercer.

One function of macropinocytosis is engulfment of apoptotic debris, which is triggered by contact between the engulfing cell and membranes with exposed phosphatidylserines (PS), which are normally hidden on the inner membrane surface of cells. The vaccinia membrane is known to be rich in PS, and when the authors blocked PS, infectivity dropped; the virus still bound to cells, but no blebbing or entry occurred. "It's a beautiful way to invade a lot of different cell types," Mercer says, "because uptake of phosphatidylserine is such a general mechanism. The virus is taking advantage of a system the cell can't get rid of." Formula

Mercer, J., and A. Helenius. 2008. Science. 320:531–535.[Abstract/Free Full Text]



Richard Robinson

rrobinson{at}nasw.org


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