HERPES-SIMPLEX VIRUS TYPE-1 TEGUMENT PROTEIN VP22 INDUCES THE STABILIZATION AND HYPERACETYLATION OF MICROTUBULES

The role of the herpes simplex virus type 1 tegument protein VP22 duri ng infection is as yet undefined. We have previously shown that VP22 h as the unusual property of efficient intercellular transport, such tha t the protein spreads from single expressing cells into large numbers of surrounding cells. We also noted that in cells expressing VP22 by t ransient transfection, the protein localizes in a distinctive cytoplas mic filamentous pattern. Here we show that this pattern represents a c olocalization between VP22 and cellular microtubules. Moreover, we sho w that VP22 reorganizes microtubules into thick bundles which are easi ly distinguishable from nonbundled microtubules. These bundles are hig hly resistant to microtubule-depolymerizing agents such as nocodazole and incubation at 4 degrees C, suggesting that VP22 has the capacity t o stabilize the microtubule network. In addition, we show that the mic rotubules contained in these bundles are modified by acetylation, a ma rker for microtubule stability. Analysis of infected cells by both imm unofluorescence and measurement of microtubule acetylation further sho wed that colocalization between VP22 and microtubules, and induction o f microtubule acetylation, also occurs during infection. Taken togethe r, these results suggest that VP22 exhibits the properties of a classi cal microtubule-associated protein (MAP) during both transfection and infection. This is the first demonstration of a MAP encoded by an anim al virus.