HIV-1 envelope-CXCR4 signaling triggers cofilin activation to promote cortical actin dynamics and HIV nuclear migration.

(A) HIV-1 envelope binding to CD4 and the chemokine coreceptor, CXCR4, triggers membrane fusion and signaling transduction. The initial viral contact with CD4 and then CXCR4 may trigger rapid actin polymerization to facilitate CD4/CXCR4 cocapping for fusion and entry. Following fusion, the viral preintegration complex (PIC) may be directly anchored onto F-actin to facilitate reverse transcription. Subsequent actin activity mediated by cofilin activation through CXCR4 promotes viral nuclear migration. (B) Model of HIV PIC migration along the cortical actin filaments. It is possible that cofilin activation increases actin treadmilling, which promotes the movement of the viral PIC across the cortical actin barrier, allowing PIC to gain access to the perinuclear or nuclear region. The number is arbitrarily assigned to an actin monomer to demonstrate the actin movement during treadmilling. (Figure 3 is modified from [44] with permission).