How to engage Cofilin

Abstract

In HIV-infected people, resting CD4+ T cells are the main reservoir of latent virus and the reason for the failure of drug therapy to cure HIV infection. Still, we do not have a complete understanding of the factors regulating HIV replication in these cells. A recent paper in Cell describes a new trick that the virus uses to infect resting T cells. Interaction between the viral gp120 and cellular HIV co-receptor, CXCR4, during viral entry initiates signaling that activates cofilin, the main regulator of actin polymerization. As a result of this activation, actin is depolymerized, thus destroying the natural barrier to HIV replication. I discuss implications of this study for our understanding of HIV biology and development of novel anti-HIV therapeutic approaches.

Figure 1

A model depicting actin regulation by cofilin during HIV-1 infection of resting T cell. Interactions between the key factors involved in regulation of cortical actin are shown in the context of HIV-1 infection. HIV-induced signaling from CXCR4 activates phosphatase which dephosphorylates and activates cofilin. This leads to depolymerization of F-actin, releasing HIV-1 reverse transcription complex and promoting its translocation towards the nucleus. Steps requiring additional studies, such as involvement of CCR5 in cofilin activation, regulation of a switch between activation of cofilin kinase and phosphatase, the role of F-actin in HIV reverse transcription and nuclear translocation are marked by question marks. See text for details.