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Journal of Bacteriology and Virology, 2019. 49(2), 69-80, DOI: https://doi.org/10.4167/jbv.2019.49.2.69
Diverse Effects of Small Molecule Inhibitors on Actin Cytoskeleton Dynamics in HIV-1 Infection
YoungHyun Shin, Byeong-Sun Choi;Kyung-Chang Kim;Kisoon Kim;Cheol-Hee Yoon
The dynamics of the actin cytoskeleton plays a pivotal role in the process of celldivision, the transportation of organelles, vesicle trafficking and cell movement.HIV-1 (Human immunodeficiency virus type 1) hijacks the actin dynamics networkduring the viral entry and migration of the pre-integration complex (PIC) into thenucleus. Actin dynamics linked to HIV-1 has emerged as a potent therapeutic targetagainst HIV infection. Although some inhibitors have been intensely analyzed withregard to HIV-1 infection, their effects are sometimes disputed and the exactmechanisms for actin dynamics in HIV infection have not been well elucidated. Inthis study, the small molecules regulating HIV-1 infection from diverse inhibitors ofthe actin dynamic network were screened. Two compounds, including ChaetoglobosinA and CK-548, were observed to specifically bar the viral infection, while thecytochalasin family, 187-1, N-WASP inhibitor, Rho GTPase family inhibitors(EHop-016, CID44216842, and ML-141) and LIMK inhibitor (LIM domain kinaseinhibitor) increased the viral infection without cytotoxicity within a range of ~ μM.However, previously known inhibitory compounds of HIV-1 infection, such asLatrunculin A, Jasplakinolide, Wiskostatin and Swinholide A, exhibited either aninhibitory effect on HIV-1 infection combined with severe cytotoxicity or showed noeffects. Our data indicate that Chaetoglobosin A and CK-548 have considerablepotential for development as new therapeutic drugs for the treatment of HIVinfection. In addition, the newly identified roles of Cytochalasins and some inhibitorsof Rho GTPase and LIMK may provide fundamental knowledge for understandingthe complicated actin dynamic pathway when hijacked by HIV-1. Remarkably, thenewly defined action modes of the inhibitors may be helpful in developing potentanti-HIV drugs that target the actin network, which are required for HIV infection.
- DOI: https://doi.org/10.4167/jbv.2019.49.2.69
- ISBN or ISSN: 1598-2467
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.