title: Influenza A virus neuraminidase limits viral superinfection.
abstract: 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 alpha-2,3- and alpha-2,6-linked sialic acid 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Southborough, Massachusetts 01772, USA.
authors.forename: I-Chueh
authors.initials: IC
authors.lastname: Huang
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sui
authors.forename: Wayne
authors.initials: W
authors.lastname: Marasco
authors.forename: Hyeryun
authors.initials: H
authors.lastname: Choe
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D006388:Hemagglutinins / Q000235:genetics / Q000502:physiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D053139:Oseltamivir / Q000494:pharmacology; D014762:Viral Interference; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology*; D053243:Zanamivir / Q000494:pharmacology; D000086082:Viroporin Proteins
chemical_list: D000998:Antiviral Agents; D006388:Hemagglutinins; D009439:Neuraminidase; D053139:Oseltamivir; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D053243:Zanamivir; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins