title: The N-terminal fragment of PA subunit of the influenza A virus effectively inhibits ribonucleoprotein (RNP) activity via suppression of its RNP expression.
abstract: The influenza RNP, which is formed from PB1, PB2, PA, NP subunits, and vRNA, is autonomously replicated and transcribed in the infected cell. The simplest method to inhibit RNP activity is to impair the formation of the RNP. Thereupon we confirmed whether the peptides/fragments mimicking one of RNP components can interfere with their formation. During the process of this inhibitory study we found interesting suppression of protein expression of the RNP components by the N-terminal fragment of PA subunit. Especially, we found two residues (D108 and K134) on the fragment that were critical for the suppression. Furthermore, we determined the combination of three amino acids (P28, M86 and E100) on the fragment that are important for the strong suppression, and identified the minimum essential region (residues from 1 to 188) of the PA subunit that allowed its suppression. Our findings indicate that the N-terminal fragment of PA subunit may become one of candidates for an effective inhibitor of influenza RNP activity.
authors: Department of Infection Control and Prevention, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors: Yusaku
authors: Y
authors: Uemura
authors: Department of Infection Control and Prevention, Kurume University School of Medicine, Kurume, Fukuoka, Japan. Electronic address: takahito@med.kurume-u.ac.jp.
authors: Takahito
authors: T
authors: Kashiwagi
authors: Department of Infection Control and Prevention, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors: Koyu
authors: K
authors: Hara
authors: Department of Infection Control and Prevention, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors: Yoko
authors: Y
authors: Nakazono
authors: Department of Infection Control and Prevention, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors: Nobuyuki
authors: N
authors: Hamada
authors: Department of Infection Control and Prevention, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors: Hiroshi
authors: H
authors: Watanabe
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D012261:Ribonucleoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D021122:Protein Subunits; D012261:Ribonucleoproteins; D014764:Viral Proteins
keywords: Influenza A virus; Inhibitor; PA subunit; RNA polymerase; Ribonucleoprotein