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Vol. 17, Issue 8, 3557-3568, August 2006

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Infection with Replication-deficient Adenovirus Induces Changes in the Dynamic Instability of Host Cell Microtubules

Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015

Submitted September 11, 2005; Revised May 24, 2006; Accepted June 1, 2006
Monitoring Editor: J. Richard McIntosh

Adenovirus translocation to the nucleus occurs through a well characterized minus end-directed transport along microtubules. Here, we show that the adenovirus infection process has a significant impact on the stability and dynamic behavior of host cell microtubules. Adenovirus-infected cells had elevated levels of acetylated and detyrosinated microtubules compared with uninfected cells. The accumulation of modified microtubules within adenovirus-infected cells required active RhoA. Adenovirus-induced changes in microtubule dynamics were characterized at the centrosome and at the cell periphery in living cells. Adenovirus infection resulted in a transient enhancement of centrosomal microtubule nucleation frequency. At the periphery of adenovirus-infected cells, the dynamic instability of microtubules plus ends shifted toward net growth, compared with the nearly balanced growth and shortening observed in uninfected cells. In infected cells, microtubules spent more time in growth, less time in shortening, and underwent catastrophes less frequently compared with those in uninfected cells. Drug-induced inhibition of Rac1 prevented most of these virus-induced shifts in microtubule dynamic instability. These results demonstrate that adenovirus infection induces a significant stabilizing effect on host cell microtubule dynamics, which involve, but are not limited to, the activation of the RhoGTPases RhoA and Rac1.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: James Warren ( jaw8{at}lehigh.edu)

Abbreviations used: Ad, adenovirus; Ad-AF555, adenovirus conjugated to Alexa Fluor 555; ASFV, African swine fever virus; FAK, focal adhesion kinase; HHV, human herpesvirus; HSV, herpes simplex virus; k_c, catastrophe frequency; k_r, rescue frequency; MT, microtubule; PI3K, phosphoinositide 3-kinase.