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