Use of REV-dependent HIV reporter cell, REV-CEM-GFP/Luc, helps lead to discovering small molecular inhibitors that block the HIV host dependency factor LIMK1

The actin cytoskeleton plays an important role in HIV entry, intracellular migration, and viron release. LIM domain kinase (LIMK) regulates actin cytoskeleton by phosphorylating cofilin.  HIV can gain entry into T-cells by hijacking the LIMK/cofilin pathway.  Conversely, inhibiting LIMK activity has been shown to block HIV nuclear migration,  virion release, and cell-to-cell transmission.  Yi et al (2017) recently published an article describing the design, synthesis, and screening of specific small molecule LIMK inhibitors blocking HIV-1, and other viruses.  In the process, the team used an HIV Rev-dependent cell line, REV-CEM-GFP/Luc, to screen the LIMK inhibitors, and discovered R10015 that blocks HIV DNA synthesis, nuclear entry, and virion release through blocking LIMK activity. The high HIV-specificity of the Rev-dependent reporter allowed the researchers to distinguish specific anti-HIV activity versus non-specific ones.

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