JVI Accepts, published online ahead of print on 6 August 2008

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J. Virol. doi:10.1128/JVI.01226-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Oseltamivir-Resistant Influenza A Viruses Transmit Efficiently Among Guinea Pigs by Direct Contact but not by Aerosol

Nicole M. Bouvier, Anice C. Lowen, and Peter Palese^*

Division of Infectious Diseases, Department of Medicine, and Department of Microbiology, Mount Sinai School of Medicine, New York, New York

^* To whom correspondence should be addressed. Email: peter.palese{at}mssm.edu.

Influenza viruses resistant to the neuraminidase inhibitor oseltamivir arise under drug selection pressure both in vitro and in vivo. Several mutations in the active site of the viral neuraminidase (NA) are known to confer relative resistance to oseltamivir, and influenza viruses with certain oseltamivir-resistance mutations have been shown to transmit efficiently among co-caged ferrets. However, it is not known whether NA mutations alter the mode of transmission of drug-resistant influenza virus. Here we demonstrate that recombinant human influenza A/H3N2 viruses with and without oseltamivir-resistance mutations (NA-E119V and NA-E119V+I222V) have similar in ovo growth kinetics and infectivity in guinea pigs. These viruses also transmit efficiently by the contact route among co-caged guinea pigs, as in the ferret model. However, in an aerosol transmission model, in which guinea pigs are caged separately, the oseltamivir-resistant viruses transmit poorly or not at all; in contrast, the oseltamivir-sensitive virus transmits efficiently, even in the absence of direct contact. The present results suggest that oseltamivir-resistance mutations reduce aerosol transmission of influenza virus, which could have implications for public health measures taken in the event of an influenza pandemic.

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