Low-pH Stability of Influenza A Virus Sialidase Contributing to Virus Replication and Pandemic

• Takahashi Tadanobu

  Department of Biochemistry, School of Pharmaceutical Sciences, 
University of Shizuoka

• Suzuki Takashi

  Department of Biochemistry, School of Pharmaceutical Sciences, 
University of Shizuoka

抄録

The spike glycoprotein neuraminidase (NA) of influenza A virus (IAV) has sialidase activity that cleaves the terminal sialic acids (viral receptors) from oligosaccharide chains of glycoconjugates. A new antigenicity of viral surface glycoproteins for humans has pandemic potential. We found “low-pH stability of sialidase activity” in NA. The low-pH stability can maintain sialidase activity under acidic conditions of pH 4–5. For human IAVs, NAs of all pandemic viruses were low-pH-stable, whereas those of almost all human seasonal viruses were not. The low-pH stability was dependent on amino acid residues near the active site, the calcium ion-binding site, and the subunit interfaces of the NA homotetramer, suggesting effects of the active site and the homotetramer on structural stability. IAVs with the low-pH-stable NA showed much higher virus replication rates than those of IAVs with low-pH-unstable NA, which was correlated with maintenance of sialidase activity under an endocytic pathway of the viral cell entry mechanism, indicating contribution of low-pH stability to high replication rates of pandemic viruses. The low-pH-stable NA of the 1968 H3N2 pandemic virus was derived from the low-pH-stable NA of H2N2 human seasonal virus, one of two types classified by both low-pH stability in N2 NA and a phylogenetic tree of N2 NA genes. The 2009 H1N1 pandemic virus acquired low-pH-stable NA by two amino acid substitutions at the early stage of the 2009 pandemic. It is thought that low-pH stability contributes to infection spread in a pandemic through enhancement of virus replication.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 38 (6), 817-826, 2015

  公益社団法人 日本薬学会

キーワード

• influenza virus
• sialidase
• low-pH stability
• virus replication
• pandemic

詳細情報

• CRID: 1390001204634184064
• NII論文ID: 130005072670
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b15-00120
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 026408141
• PubMed: 26027822
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026408141
• Web Site: https://www.jstage.jst.go.jp/article/bpb/38/6/38_b15-00120/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016026441
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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