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

26 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

Fingerprint

Karyopherins
Cell Nucleus Active Transport
Viruses
HIV-1
Hematoxylin
Virus Replication
Therapeutics
Human Immunodeficiency Virus Proteins
Viral Proteins
Macrophages
Accessories
Antiviral Agents
Real-Time Polymerase Chain Reaction
HIV
Genes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin α interactions as a novel HIV-1 therapy. / Suzuki, Tatsunori; Yamamoto, Norio; Nonaka, Mizuho; Hashimoto, Yoshie; Matsuda, Go; Takeshima, Shin nosuke; Matsuyama, Megumi; Igarashi, Tatsuhiko; Miura, Tomoyuki; Tanaka, Rie; Kato, Shingo; Aida, Yoko.

In: Biochemical and Biophysical Research Communications, Vol. 380, No. 4, 20.03.2009, p. 838-843.

Research output: Contribution to journalArticle

Suzuki, T, Yamamoto, N, Nonaka, M, Hashimoto, Y, Matsuda, G, Takeshima, SN, 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, vol. 380, no. 4, pp. 838-843. https://doi.org/10.1016/j.bbrc.2009.01.180
Suzuki, Tatsunori ; Yamamoto, Norio ; Nonaka, Mizuho ; Hashimoto, Yoshie ; Matsuda, Go ; Takeshima, Shin nosuke ; Matsuyama, Megumi ; Igarashi, Tatsuhiko ; Miura, Tomoyuki ; Tanaka, Rie ; Kato, Shingo ; Aida, Yoko. / Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin α interactions as a novel HIV-1 therapy. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 380, No. 4. pp. 838-843.
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