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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
figure 1

Endocytosis of CXCR4 analyzed by Western blot.

Figure 2
figure 2

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

References

  1. Yoder A, Yu D, Dong L, Iyer SR, Xu X, Kelly J, Liu J, Wang W, Vorster PJ, Agulto L, Stephany DA, Cooper JN, Marsh JW, Wu Y: HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells. Cell. 134: 782-92. 10.1016/j.cell.2008.06.036.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Vorster, P.J., Yoder, A., Yu, D. et al. Dichotomous effects of the cofilin kinase LIMK1 on the early steps of HIV-1 infection of CD4 T cells. Retrovirology 6, O8 (2009). https://doi.org/10.1186/1742-4690-6-S2-O8

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  • DOI: https://doi.org/10.1186/1742-4690-6-S2-O8

Keywords

  • Actin Cytoskeleton
  • Actin Dynamic
  • Transient Activation
  • Cortical Actin
  • Cell Chemotaxis