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Science 21 June 2002:
Vol. 296. no. 5576, pp. 2218 - 2222
DOI: 10.1126/science.1070585
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Reports

Visualization and Functional Analysis of RNA-Dependent RNA Polymerase Lattices

John M. Lyle,1* Esther Bullitt,2* Kurt Bienz,3 Karla Kirkegaard1dagger

Positive-strand RNA viruses such as poliovirus replicate their genomes on intracellular membranes of their eukaryotic hosts. Electron microscopy has revealed that purified poliovirus RNA-dependent RNA polymerase forms planar and tubular oligomeric arrays. The structural integrity of these arrays correlates with cooperative RNA binding and RNA elongation and is sensitive to mutations that disrupt intermolecular contacts predicted by the polymerase structure. Membranous vesicles isolated from poliovirus-infected cells contain structures consistent with the presence of two-dimensional polymerase arrays on their surfaces during infection. Therefore, host cytoplasmic membranes may function as physical foundations for two-dimensional polymerase arrays, conferring the advantages of surface catalysis to viral RNA replication.

1 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, USA.
3 Institute for Medical Microbiology, University of Basel, CH-4003 Basel, Switzerland.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: karlak{at}leland.stanford.edu

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