Pinosomes (arrow) form in Ad2-infected cells.

Many virus species are taken into their host via receptor-mediated endocytosis, after which the virus particle is temporarily contained within endosomes. For genome propagation, most viruses must escape into the cytosol. New results from Meier et al. (page 1119) explain how Adenovirus type 2 (Ad2), one of the most rapidly escaping viruses known, tricks the cell into helping it break free.

Meier et al. first show that Ad2 enters in clathrin- dependent endosomes. But subsequent escape from the endosomes is dependent on pinocytosis, a process by which extracellular material is taken in within enclosed lamellipodia at ruffling membranes. Ad2 initiates integrin signaling and thus pinocytosis at the plasma membrane. It also triggers pinosomal lysis, again apparently from the cell surface, as internalized viral particles were not required.

The virus is not taken in by pinocytosis, so what is the function of the pinosomes? Pinosomes in maturing dendritic cells leak their contents into the cytoplasm; perhaps Ad2 uses integrin signaling to stimulate the formation of similar leaky compartments. The group is now examining whether virus-loaded endosomes and pinosomes fuse, thereby shuffling virus into a compartment that can be sufficiently destabilized for viral escape. In any case, efficient gene expression from many viral vectors used for gene therapy will require more than just vector endocytosis. ▪