The Exploitation of Rab Proteins by Viral Pathogens

Rab proteins play a fundamental role in regulating the transport of vesicles between intracellular donor and acceptor compartments. A large class of proteins referred to as small GTPases, includes Rab, Ras, Rac, Ran, Rho, Arf, and Sar proteins. GTPases cycle between binding GDP or GTP. Conformational changes associated with the nucleotide binding state of GTPases facilitate the interaction of GTPases with “effector” molecules. The “effector” molecules then allow for downstream actions of GTPases. Rab proteins are considered the “master regulators” of intracellular vesicular trafficking, providing both temporal and spatial specificity in vesicular transport and that regulation is dependent on the “effector” molecules binding to any particular Rab protein.

Viruses, as intracellular parasites, depend on host cells for propagation and dissemination. Host cell mechanisms that allow viral entry, facilitate viral replication, and enable viral egress, have been targeted for exploitation by viral pathogens. Emerging evidence demonstrates that viruses have evolved numerous strategies to modulate Rab proteins’ functions. Strategies range from enhancing viral uptake and transport to replication-competent intracellular locales to altering host cell transcription to altering cellular processes to permit viral egress from host cells. Understanding the molecular mechanisms by which viral pathogens utilize host cells to their own advantage will enable the future development of strategies to combat viral pathogenesis. Furthermore, delineating viral mechanisms used to alter Rab function will potentially identify unknown cellular mechanisms that play important roles in intracellular vesicular transport.