F11L-mediated inhibition of RhoA-mDia signaling stimulates microtubule dynamics during vaccinia virus infection.
Microtubules play an important role in the transport of viral pathogens during the establishment of their infection cycles. The microtubule cytoskeleton also facilitates efficient release of newly assembled progeny at later stages of infection. However, the precise effects of viral infection on microtubule dynamics are not understood. Using live-cell imaging, we show that vaccinia virus stimulates increases in peripheral microtubule dynamics at 8 hr postinfection. Infection also increases the frequency with which microtubule tips reach the cell cortex and reduces the acetylation of peripheral microtubules consistent with their increased dynamics. These virus-induced changes in peripheral microtubule dynamics are independent of the GTPases Rac and Cdc42, which are known stimulators of microtubule dynamics in uninfected cells. They do, however, require F11L-mediated inhibition of signaling via the GTPase RhoA and its effector, mDia. We suggest that increases in peripheral microtubule dynamics and cortical targeting contribute to enhanced virus release.
Arakawa
Yoshiki
Y
Cell Motility Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Cordeiro
João V
JV
Way
Michael
M
D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D014616:Vaccinia virus / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors*
D014764:Viral Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein