Dichotomous effects of the cofilin kinase LIMK1 on the early steps of HIV-1 infection of CD4 T cells

We have previously demonstrated that binding of HIV-1 to the chemokine coreceptor, CXCR4, on resting CD4 T cells activates an actin-depolymerizing factor cofilin to promote the cortical actin dynamic critical for HIV latent infection [1]. The LIM domain kinase 1 (LIMK1) directly phosphorylates cofilin and regulates the actin cytoskeleton. Here, we investigated the role of LIMK1 in HIV-1 infection of resting CD4 T cells and found that HIV-1 infection triggered a rapid, transient activation of LIMK1. We also used siRNA knockdown to inhibit LIMK1 activity and found that knockdown of LIMK1 caused a decrease of F-actin and T cell chemotaxis. LIMK1 also had dichotomous effects on the chemokine coreceptor CXCR4 cycling (Figure 1) and viral DNA synthesis (Figure 2). Our findings are consistent with a model suggesting a multi-functional role of the cortical actin in mediating chemokine coreceptor density, HIV-1 DNA synthesis and intracellular migration.

Figure 1

Endocytosis of CXCR4 analyzed by Western blot.

Figure 2

Real-time PCR analysis HIV-1DNA synthesis in LIMK1 knockdown cells (007-LIMK knockdown cells, NTC-control cells).