PEARLS A 21st Century Perspective of Poliovirus Replication Nicolas Leveque 1 , Bert L. Semler 2 * 1 Clinical and Molecular Virology Unit (EA-4684 CardioVir), School of Medicine, University of Reims Champagne-Ardenne, Reims, France, 2 Center for Virus Research, Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, California, United States of America * blsemler@uci.edu Why Poliovirus Replication Has Been Studied for More Than 50 Years OPEN ACCESS Citation: Leveque N, Semler BL (2015) A 21st Century Perspective of Poliovirus Replication. PLoS Pathog 11(6): e1004825. doi:10.1371/journal. ppat.1004825 Editor: Katherine R. Spindler, University of Michigan Medical School, UNITED STATES Published: June 4, 2015 Copyright: © 2015 Leveque, Semler. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Research in the authors’ lab was supported by Public Health Service grants AI022693, AI026765, and AI110782 from the National Institutes of Health (to BLS). NL is supported by a Marie Curie International Outgoing Fellowship for Career Development from the European Commission and by grants from the Philippe Foundation and the Champagne-Ardenne region. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Poliovirus is the etiologic agent of poliomyelitis, an acute flaccid paralysis affecting 1%–2% of infected patients and, on rare occasions, causing death by paralyzing muscles that control the throat or breathing. A striking feature of infection is lifelong disabilities that may affect survi- vors of the acute disease. Transmitted by the fecal—oral and oral—oral route, this virus (three serotypes) was one of the most feared pathogens in industrialized countries during the 20th century affecting hundreds of thousands of children every year, via outbreaks during warm summer months. Although there are highly effective vaccines to control poliomyelitis, it re- mains endemic in a few countries, from which spread and outbreaks continue to occur throughout the world. Since its discovery in 1908, poliovirus has been intensively studied to better understand and control this formidable pathogen. The history of poliovirus is not, how- ever, limited to the fight against the disease. Poliovirus replication studies also have played important roles in the development of modern virology since poliovirologists and, more gener- ally, picornavirologists have been pioneers in many domains of molecular virology. Poliovirus was, for example, the first animal RNA virus to have its complete genome sequence deter- mined, the first RNA animal virus for which an infectious clone was constructed, and, along with the related rhinovirus, the first human virus that had its three-dimensional structure solved by X-ray crystallography. Indeed, the history of over half a century of poliovirus replica- tion studies is marked by major discoveries, many of which are summarized here and illustrat- ed in Fig 1. 1950–1970: The Early Years In 1949, John Enders, Thomas Weller, and Frederick Robbins performed a landmark study showing that poliovirus could be propagated in cultured, non-neural human cells that did not correspond to the tissues infected during the disease [1]. Not only did these Nobel Prize-win- ning studies pave the way for the development of highly effective vaccines against poliovirus, but they also opened the door for virologists to study the molecular mechanisms of poliovirus replication in cultured cells that were much more readily manipulated than neural tissue. Iso- lated poliovirus genomic RNA was then shown to be infectious for susceptible HeLa cells in monolayers, demonstrating that the viral genome itself is the carrier of the biological activity responsible for infection [2]. John Holland and coworkers then reproduced this experiment with normally nonsusceptible cells, demonstrating that the block to poliovirus growth in PLOS Pathogens | DOI:10.1371/journal.ppat.1004825 June 4, 2015
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