Abstract

When viruses enter host cells most of them follow a stepwise program that involves attachment, activation of signaling pathways, endocytosis, penetration into the cytosol, intracellular transport, and finally uncoating of the viral genome. Since these steps depend on cellular functions, hundreds of cellular proteins inadvertently end up assisting the viruses. Using high-end light microscopy, automated siRNA and drug screening as well as biochemical and biophysical approaches, we have analyzed the cell biology of entry of viruses from different families. We find five distinct routes with penetration occurring in the plasma membrane, early endosomes, maturing and late endosomes, macropinosomes, and the ER. I will review the general concepts, and describe in more detail the entry strategies used by influenza A and vaccinia virus.