Possible mechanisms and signaling pathways of chemokines, chemokine receptors, and other proteins affecting the modulation of actin during human immunodeficiency virus (HIV) infection. HIV gp120 binding to the CXCR4 or CCR5 co-receptor, thereby mimicking the CXCL12/CXCR4 interaction, induces actin-related signaling. In addition, CXCL10, CCL19, CCL21, C–C motif chemokine ligand 20 (CCL20), and C–C motif chemokine ligand 2 (CCL2), which are elevated during HIV infection, bind to their receptors and thereby activate actin-related signaling (56, 69, 100, 105). Moesin (118, 119), filamin-A (120), and gelsolin (121) also promote actin-related signaling pathways. Two major actin-related signaling pathways, such as LIMK1–cofilin (122) and WAVE2–Arp2/3 (123), induce polymerization and depolymerization of actin, further leading to rearrangement of the cytoskeleton, and thus benefit HIV fusion, entry, nuclear integration, release, and, ultimately, transmission. By contrast, Slit2N binding to Robo1 (124) could inhibit the two major actin-related signaling pathways. R10015 (125), CK548 (126), Abl kinase inhibitor (127), genistein (110, 112), and sunitinib (110) can also inhibit actin-related signaling.