title: A conserved influenza A virus nucleoprotein code controls specific viral genome packaging.
abstract: Packaging of the eight genomic RNA segments of influenza A viruses (IAV) into viral particles is coordinated by segment-specific packaging sequences. How the packaging signals regulate the specific incorporation of each RNA segment into virions and whether other viral or host factors are involved in this process is unknown. Here, we show that distinct amino acids of the viral nucleoprotein (NP) are required for packaging of specific RNA segments. This was determined by studying the NP of a bat influenza A-like virus, HL17NL10, in the context of a conventional IAV (SC35M). Replacement of conserved SC35M NP residues by those of HL17NL10 NP resulted in RNA packaging defective IAV. Surprisingly, substitution of these conserved SC35M amino acids with HL17NL10 NP residues led to IAV with altered packaging efficiencies for specific subsets of RNA segments. This suggests that NP harbours an amino acid code that dictates genome packaging into infectious virions.
authors.affiliation: Institute of Virology, University Medical Center Freiburg, 79104 Freiburg, Germany.|Spemann Graduate School of Biology and Medicine, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Étori Aguiar
authors.initials: ÉA
authors.lastname: Moreira
authors.affiliation: Institute of Virology, University Medical Center Freiburg, 79104 Freiburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Weber
authors.affiliation: Institute of Virology, University Medical Center Freiburg, 79104 Freiburg, Germany.|Spemann Graduate School of Biology and Medicine, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Hardin
authors.initials: H
authors.lastname: Bolte
authors.affiliation: Institute of Virology, Philipps-Universität Marburg, 35043 Marburg, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Kolesnikova
authors.affiliation: Institute of Virology, University Medical Center Freiburg, 79104 Freiburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giese
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15217, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Lakdawala
authors.affiliation: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Beer
authors.affiliation: Institute of Virology and Immunology (IVI), 3147 Mittelhäusern, Switzerland.
authors.forename: Gert
authors.initials: G
authors.lastname: Zimmer
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Institute of Virology, University Medical Center Freiburg, 79104 Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schwemmle
authors.affiliation: Institute of Virology, University Medical Center Freiburg, 79104 Freiburg, Germany.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Juozapaitis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002685:Chiroptera / Q000821:virology; D017124:Conserved Sequence; D016679:Genome, Viral; D008958:Models, Molecular; D009154:Mutation; D009698:Nucleoproteins / Q000235:genetics*; D009975:Orthomyxoviridae / Q000235:genetics*; D011487:Protein Conformation; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D009698:Nucleoproteins