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Virus entry by macropinocytosis

Abstract

As obligatory intracellular parasites, viruses rely on host-cell functions for most aspects of their replication cycle. This is born out during entry, when most viruses that infect vertebrate and insect cells exploit the endocytic activities of the host cell to move into the cytoplasm. Viruses belonging to vaccinia, adeno, picorna and other virus families have been reported to take advantage of macropinocytosis, an endocytic mechanism normally involved in fluid uptake. The virus particles first activate signalling pathways that trigger actin-mediated membrane ruffling and blebbing. Usually, this is followed by the formation of large vacuoles (macropinosomes) at the plasma membrane, internalization of virus particles and penetration by the viruses or their capsids into the cytosol through the limiting membrane of the macropinosomes. We review the molecular machinery involved in macropinocytosis and describe what is known about its role in virus entry.

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Figure 1: Endocytic pathways used by viruses.
Figure 2: Macropinosome formation is an actin based process.
Figure 3: Signalling during RTK-activated macropinocytosis.
Figure 4: Vaccinia virus-induced macropinocytosis involves blebbing of the plasma membrane.

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Acknowledgements

We apologize to those individuals whose work we were unable to discuss due to space limitations. We thank members of the Helenius laboratory for thoughtful discussion. Funding was obtained from ETH Zurich and EMBO.

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Correspondence to Ari Helenius.

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Mercer, J., Helenius, A. Virus entry by macropinocytosis. Nat Cell Biol 11, 510–520 (2009). https://doi.org/10.1038/ncb0509-510

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