Rho-GTPases subfamily: cellular defectors orchestrating viral infection.

Abstract

Ras homolog gene family-guanosine triphosphatases (Rho-GTPases), key molecular switches regulating cytoskeletal dynamics and cellular signaling, play a pivotal role in viral infections by modulating critical processes such as viral entry, replication, and release. This review elucidates the intricate mechanisms through which Rho-GTPases, via interactions with guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and other signaling pathways, including the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), rat sarcoma (Ras), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, facilitate viral pathogenesis. Specific viruses, such as influenza A virus (IAV), herpesviruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), exploit Rho-GTPase-mediated cytoskeletal reorganization to enhance infectivity. For example, Rho-GTPases promote actin remodeling and membrane fusion, which are essential for viral entry and intracellular transport. Furthermore, Rho-GTPases modulate immune responses, often suppressing antiviral defenses to favor viral replication. Despite these insights, the molecular mechanisms underlying Rho-GTPase regulation during viral infections remain incompletely understood. Future research should focus on delineating the precise roles of Rho-GTPases in distinct viral life cycles, uncovering novel regulatory mechanisms, and developing targeted antiviral therapies that selectively inhibit Rho-GTPase signaling without compromising host cell functions. Such advancements could pave the way for broad-spectrum antiviral strategies, particularly against viruses that heavily rely on cytoskeletal manipulation for infection.