Filament-Producing Mutants of Influenza A/Puerto Rico/8/1934 (H1N1) Virus Have Higher Neuraminidase Activities than the Spherical Wild-Type

• Type of Material: Article
• Authors: Jill Seladi-Schulman, Emory University; Patricia J. Campbell, Emory University; Suganthi Suppiah, Emory University; John Steel, Emory University; Anice Carmen Lowen, Emory University
• Language: English
• Date: 2014-11-10
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Seladi-Schulman et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0112462
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 9
• Issue: 11
• Start Page: e112462
• End Page: e112462
• Grant/Funding Information: This work was funded by the National Institutes of Health/National Institute of Allergy and Infectious Disease under Centers for Excellence in Influenza Research and Surveillance (CEIRS) contract number HHSN266200700006C.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: IN-VIVO; M SEGMENT; CONTACT; VIRAL MORPHOLOGY; M1; STRAINS; VIRIONS; A VIRUS; Science & Technology - Other Topics; HEMAGGLUTININ; Multidisciplinary Sciences; Science & Technology; PARTICLE FORMATION
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Influenza virus exhibits two morphologies - spherical and filamentous. Strains that have been grown extensively in laboratory substrates are comprised predominantly of spherical virions while clinical or low passage isolates produce a mixture of spheres and filamentous virions of varying lengths. The filamentous morphology can be lost upon continued passage in embryonated chicken eggs, a common laboratory substrate for influenza viruses. The fact that the filamentous morphology is maintained in nature but lost in favor of a spherical morphology in ovo suggests that filaments confer a selective advantage within the infected host that is not necessary for growth in laboratory substrates. Indeed, we have recently shown that filament-producing variant viruses are selected upon passage of the spherical laboratory strain A/ Puerto Rico/8/1934 (H1N1) [PR8] in guinea pigs. Toward determining the nature of the selective advantage conferred by filaments, we sought to identify functional differences between spherical and filamentous particles. We compared the wildtype PR8 virus to two previously characterized recombinant PR8 viruses in which single point mutations within M1 confer a filamentous morphology. Our results indicate that these filamentous PR8 mutants have higher neuraminidase activities than the spherical PR8 virus. Conversely, no differences were observed in HAU:PFU or HAU:RNA ratios, binding avidity, sensitivity to immune serum in hemagglutination inhibition assays, or virion stability at elevated temperatures. Based on these results, we propose that the pleomorphic nature of influenza virus particles is important for the optimization of neuraminidase functions in vivo.