Figure 4.

Actin-related changes in cellular behavior induced by HIV in relevant cell types. Coordinated manipulation of actin regulators results in global and cell-type specific changes in cellular morphology and motility that contribute to viral spread, impairment of immune function and HIV comorbidities. Many of these changes can be mapped to specific HIV accessory proteins, which act as master regulators of the cytoskeleton. Nef and Tat are expressed in HIV-infected cells but are also present extracellularly in serum and, thus, can affect both infected and uninfected cells. (a) Nef; leads to Rac1 activation in a wide range of cell types. In T-cells, this is associated with inactivation of Cofilin and severe cytoskeletal disorganization, which impairs cell migration and immunological synapse formation. In myeloid cells, Nef enhances formation of several membrane protrusions which promote cell motility and contacts with uninfected cells; (b) Tat modulates the expression of numerous genes involved in actin regulation. In T-cells, Tat interferes with chemotaxis and F-actin remodeling, whereas in monocytes it increases cell motility, chemotaxis and phagocytosis. Tat also induces expression of adhesion molecules and promotes leukocyte binding to the endothelium. Upward arrows represent enhancement of biological processes or increases in number of structures, whereas downward arrows represent impairment of processes. * = Effects also induced by HIV envelope glycoprotein (Env).