Poliovirus Protein 3A Binds and Deregulates LIS1, Causing Block of Membrane Protein Trafficking and Deregulation of Cell Division

Poliovirus infection results in resistance of infected cells to apoptotic stimuli. Viral proteins involved in such functions usually target key cellular regulators. Here we demonstrate that viral protein 3A binds and inactivates LIS1, a component of the dynein/dynactin motor complex, encoded by the gene mutated in patients with type I lissencephaly (?smooth brain‰), thus causing rapid disappearence of TNF and interferon receptors from the plasma membrane. Like 3A, truncated derivatives of LIS, acting in a dominant negative manner, deregulate endoplasmatic reticilum -to-Golgi vesicular transport and eliminate unstable receptors from the cell surface. Protein 3A locks Golgi-targeted YFP in endoplasmatic reticilum, while expression of LIS1 mutants results in a dispersed cytoplasmic localization of the reporter protein. LIS1 dysfunction caused by ectopic expressing 3A or LIS1 mutants, as well as by overexpression of wild type LIS1, leads to cell trap at a postmitotic stage associated with inability to undergo cytokinesis. Thus, using vural protein as a research tool, we revealed the role of cellular protein LIS1 in endoplasmatic reticilum -to-Golgi transport, maintenance of Golgi integrity and cell cycle progression.

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