title: Importance of both the coding and the segment-specific noncoding regions of the influenza A virus NS segment for its efficient incorporation into virions.
abstract: The genome of influenza A virus consists of eight single-strand negative-sense RNA segments, each comprised of a coding region and a noncoding region. The noncoding region of the NS segment is thought to provide the signal for packaging; however, we recently showed that the coding regions located at both ends of the hemagglutinin and neuraminidase segments were important for their incorporation into virions. In an effort to improve our understanding of the mechanism of influenza virus genome packaging, we sought to identify the regions of NS viral RNA (vRNA) that are required for its efficient incorporation into virions. Deletion analysis showed that the first 30 nucleotides of the 3' coding region are critical for efficient NS vRNA incorporation and that deletion of the 3' segment-specific noncoding region drastically reduces NS vRNA incorporation into virions. Furthermore, silent mutations in the first 30 nucleotides of the 3' NS coding region reduced the incorporation efficiency of the NS segment and affected virus replication. These results suggested that segment-specific noncoding regions together with adjacent coding regions (especially at the 3' end) form a structure that is required for efficient influenza A virus vRNA packaging.
authors.affiliation: Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. kawaoka@ims.u-tokyo.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Fujii
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Muramoto
authors.forename: Tokiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
authors.forename: Hideo
authors.initials: H
authors.lastname: Goto
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D001483:Base Sequence; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000254:growth & development / Q000502:physiology*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017354:Point Mutation; D022661:RNA, Untranslated / Q000235:genetics / Q000502:physiology; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000502:physiology*; D019065:Virus Assembly / Q000502:physiology*
chemical_list: C108309:NS protein, influenza virus; D022661:RNA, Untranslated; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D049452:Green Fluorescent Proteins
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