JVI Accepts, published online ahead of print on 5 March 2008

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J. Virol. doi:10.1128/JVI.00079-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Influenza A virus neuraminidase limits viral superinfection

I-Chueh Huang, Wenhui Li, Jianhua Sui, Wayne Marasco, Hyeryun Choe, and Michael Farzan^*

Department of Microbiology and Molecular Genetics, Harvard Medical School, Southborough, Massachusetts 01772; Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115; Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115

^* To whom correspondence should be addressed. Email: farzan{at}hms.harvard.edu.

Enveloped viruses use multiple mechanisms to inhibit infection of a target cell by more than one virion. These mechanisms may be of particular importance for the evolution of segmented viruses, because superinfection exclusion may limit the frequency of reassortment of viral genes. Here we show that cellular expression of influenza A virus neuraminidase (NA), but not hemagglutinin (HA) or the M2 proton pump, inhibits entry of HA-pseudotyped retroviruses. Cells infected with H1N1 or H3N2 influenza A virus were similarly refractory to HA-mediated infection and to superinfection with a second influenza A virus. Both HA-mediated entry and viral superinfection were rescued by the neuraminidase inhibitors oseltamivir carboxylate and zanamivir. These inhibitors also prevented the removal of -2,3- and -2,6-linked sialic acid (SA) observed in cells expressing NA or infected with influenza A viruses. Our data indicate that NA alone among viral proteins limits influenza A virus superinfection.