title: Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin alpha interactions as a novel HIV-1 therapy.
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 alpha, 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 alpha 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 alpha 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.
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Suzuki
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nonaka
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Go
authors.initials: G
authors.lastname: Matsuda
authors.forename: Shin-nosuke
authors.initials: SN
authors.lastname: Takeshima
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Rie
authors.initials: R
authors.lastname: Tanaka
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aida