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Journal of Virology, November 2007, p. 12543-12553, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.00755-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Modification of Cellular Autophagy Protein LC3 by Poliovirus{triangledown}

Matthew P. Taylor and Karla Kirkegaard*

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305

Received 7 April 2007/ Accepted 27 August 2007

Poliovirus infection remodels intracellular membranes, creating a large number of membranous vesicles on which viral RNA replication occurs. Poliovirus-induced vesicles display hallmarks of cellular autophagosomes, including delimiting double membranes surrounding the cytosolic lumen, acquisition of the endosomal marker LAMP-1, and recruitment of the 18-kDa host protein LC3. Autophagy results in the covalent lipidation of LC3, conferring the property of membrane association to this previously microtubule-associated protein and providing a biochemical marker for the induction of autophagy. Here, we report that a similar modification of LC3 occurs both during poliovirus infection and following expression of a single viral protein, a stable precursor termed 2BC. Therefore, one of the early steps in cellular autophagy, LC3 modification, can be genetically separated from the induction of double-membraned vesicles that contain the modified LC3, which requires both viral proteins 2BC and 3A. The existence of viral inducers that promote a distinct aspect of the formation of autophagosome-like membranes both facilitates the dissection of this cellular process and supports the hypothesis that this branch of the innate immune response is directly subverted by poliovirus.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, 299 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305. Phone: (650) 498-7075. Fax: (650) 498-7147. E-mail: karlak{at}stanford.edu

{triangledown} Published ahead of print on 5 September 2007.

Journal of Virology, November 2007, p. 12543-12553, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.00755-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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