Fig. 2

Model diagram illustrating the interaction of Rho subfamily proteins with key signaling pathways during viral infection. Upon viral binding to membrane surface receptors, a cascade of signaling events is initiated, leading to Rho protein activation through multiple pathways including PI3K/AKT, Ras, and NF-κB. Concurrently, Rho proteins suppressed by upstream regulatory molecules (e.g., PKA) can be activated through these signaling cascades. These intricate interactions ultimately converge on cytoskeletal rearrangement, which is essential for multiple stages of the viral life cycle, including viral entry, intracellular transport, replication, and subsequent release and transmission. Notably, virus-mediated manipulation of Rho activation through cytoskeletal modulation serves multiple pathogenic functions: (1) suppression of host cell proliferation and inhibition of immune cell-mediated virion phagocytosis, (2) induction of pro-inflammatory factor release from immune cells, thereby facilitating viral spread, and (3) modulation of cellular barrier permeability, particularly evident in viral penetration of the blood–brain barrier and respiratory tract epithelia. This latter function is mediated through Rho-cytoskeleton-dependent regulation of local cell permeability, creating favorable conditions for both physical pathogen translocation and establishment of local infection foci. The coordinated regulation of these processes through Rho-cytoskeleton interactions highlights the sophisticated mechanisms by which viruses exploit host cell signaling networks to establish and propagate infection, while simultaneously evading host defense mechanisms