Vaccinia virus is closely related to the virus that causes smallpox, and was used as a vaccine to eradicate this disease. Vaccinia replicates in the cytoplasm, then moves to the cell surface from where it spreads to neighbouring cells. Virus particles have been shown to induce the formation of actin tails, on which they are thought to be propelled through the cytoplasm to reach the plasma membrane. After fusion with the membrane, virus particles are found on the tips of cellular protrusions that are driven by actin polymerization. Three recent papers now modify our view on how vaccinia moves — and implicate a second cytoskeletal transport system.

The new reports show that actin-based motility only occurs close to the cell periphery, and that the formation of actin tails seems to take place only during or after fusion of viral particles with the plasma membrane. To reach the cell periphery, however, vaccinia particles travel along microtubules in a saltatory fashion. This is the first example of a virus using both the microtubule and actin cytoskeleton to spread from cell to cell.

Rietdorf and colleagues have identified conventional kinesin as the motor that is responsible for microtubule-based transport, and show that this motor is recruited to viral particles through the tetratricopeptide (TPR) repeats in the kinesin light chain. The A36R protein, which is encoded by vaccinia and is essential for vaccinia-induced actin polymerization, is also required to recruit kinesin to virus particles and for their movement to the cell periphery. Interestingly, Rietdorf et al. found that virus particles are never associated with both kinesin and actin tails, indicating that the transition from movement along microtubules to fusion with the plasma membrane and actin-tail formation is tightly regulated. Whether A36R has any role in this, and the nature of the exact molecular link between A36R and kinesin-dependent movement, will be the subject of future studies.