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JVI Accepts, published online ahead of print on 30 April 2008
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J. Virol. doi:10.1128/JVI.00557-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A Neutralizing Antibody Blocks Adenovirus Infection by Arresting Microtubule-Dependent Cytoplasmic Transport

Jason G. Smith, Aurelia Cassany, Larry Gerace, Robert Ralston, and Glen R. Nemerow*

Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA; Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA; Department of Virology, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA

* To whom correspondence should be addressed. Email: gnemerow{at}scripps.edu.


   Abstract

Neutralizing antibodies are commonly elicited by viral infection. Most antibodies that have been characterized block early stages of virus entry occurring before membrane penetration; whereas, inhibition of late stages in entry occurring after membrane penetration has been poorly characterized. Here we provide evidence that the neutralizing anti-hexon monoclonal antibody 9C12 inhibits adenovirus infection by blocking microtubule-dependent translocation of the virus to the microtubule-organizing center following endosome penetration. These studies identify a previously undescribed mechanism by which neutralizing antibodies block virus infection, a situation that may be relevant for other non-enveloped viruses that use microtubule-dependent transport during cell entry.







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