We show that the HSV-1 structural protein VP22 has the remarkable prop
erty of intercellular transport, which is so efficient that following
expression in a subpopulation the protein spreads to every cell in a m
onolayer, where it concentrates in the nucleus and binds chromatin. VP
22 movement was observed both after delivery of DNA by transfection or
microinjection and during virus infection. Moreover, we demonstrate t
hat VP22 trafficking occurs via a nonclassical Golgi-independent mecha
nism. Sensitivity to cytochalasin D treatment suggests that VP22 utili
zes a novel trafficking pathway that involves the actin cytoskeleton.
In addition, we demonstrate intercellular transport of a VP22 fusion p
rotein after endogenous synthesis or exogenous application, indicating
that VP22 may have potential in the field of protein delivery.