Impact of the Maraviroc-Resistant Mutation M434I in the C4 Region of HIV-1 gp120 on Sensitivity to Antibody-Mediated Neutralization

• Boonchawalit Samatchaya

  Center for AIDS Research, Kumamoto University AIDS Research Center, National Institute of Infectious Diseases

• Harada Shigeyoshi

  AIDS Research Center, National Institute of Infectious Diseases

• Shirai Noriko

  Center for AIDS Research, Kumamoto University

• Gatanaga Hiroyuki

  AIDS Clinical Center, National Center for Global Health and Medicine

• Oka Shinichi

  AIDS Clinical Center, National Center for Global Health and Medicine

• Matsushita Shuzo

  Center for AIDS Research, Kumamoto University

• Yoshimura Kazuhisa

  Center for AIDS Research, Kumamoto University AIDS Research Center, National Institute of Infectious Diseases AIDS Clinical Center, National Center for Global Health and Medicine

抄録

We previously reported that a maraviroc (MVC)-resistant human immunodeficiency virus type 1variant, generated using in vitro selection, exhibited high sensitivity to several neutralizing monoclonal antibodies (NMAbs) and autologous plasma IgGs. The MVC-resistant variant acquired 4 sequential mutations in gp120: T297I, M434I, V200I, and K305R. In this study, we examined the mutation most responsible for conferring enhanced neutralization sensitivity of the MVC-resistant variant to several NMAbs and autologous plasma IgGs. The virus with the first resistant mutation, T297I, was sensitive to all NMAbs, whereas the passage control virus was not. The neutralization sensitivity of the variant greatly increased following its acquisition of the second mutation, M434I, in the C4 region. The M434I mutation conferred the greatest neutralizing sensitivity among the 4 MVC-resistant mutations. Additionally, the single M434I mutation was sufficient for the enhanced neutralization of the virus by NMAbs, autologous plasma IgGs, and heterologous sera relative to that of the parental virus.

収録刊行物

• Japanese Journal of Infectious Diseases

  Japanese Journal of Infectious Diseases 69 (3), 236-243, 2016

  国立感染症研究所 Japanese Journal of Infectious Diseases 編集委員会

キーワード

• HIV-1
• maraviroc resistant mutation
• neutralizing antibody
• enhanced neutralization
• M434I mutation

詳細情報

• CRID: 1390001206240002944
• NII論文ID: 130005151997
• NII書誌ID: AA1132885X
• DOI: 10.7883/yoken.jjid.2015.310
• ISSN: 18842836
• ISSN: 13446304
• NDL書誌ID: 027322395
• PubMed: 26166507
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027322395
• Web Site: https://www.jstage.jst.go.jp/article/yoken/69/3/69_JJID.2015.310/_pdf
• 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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