Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin α interactions as a novel HIV-1 therapy

Tatsunori Suzuki, Norio Yamamoto, Mizuho Nonaka, Yoshie Hashimoto, Go Matsuda, Shin nosuke Takeshima, Megumi Matsuyama, Tatsuhiko Igarashi, Tomoyuki Miura, Rie Tanaka, Shingo Kato, Yoko Aida

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin α, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin α interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin α interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular factor may provide a new strategy for HIV-1 therapy.

Original languageEnglish
Pages (from-to)838-843
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume380
Issue number4
DOIs
Publication statusPublished - 2009 Mar 20

Keywords

  • HIV-1 inhibitor
  • Importin α
  • Macrophage
  • Nuclear import inhibition
  • Small molecule
  • Vpr

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Suzuki, T., Yamamoto, N., Nonaka, M., Hashimoto, Y., Matsuda, G., Takeshima, S. N., Matsuyama, M., Igarashi, T., Miura, T., Tanaka, R., Kato, S., & Aida, Y. (2009). Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin α interactions as a novel HIV-1 therapy. Biochemical and Biophysical Research Communications, 380(4), 838-843. https://doi.org/10.1016/j.bbrc.2009.01.180