Beyond RGD: virus interactions with integrins

Abstract

Viruses successfully infect host cells by initially binding to the surfaces of the cells, followed by an intricate entry process. As multifunctional heterodimeric cell-surface receptor molecules, integrins have been shown to usefully serve as entry receptors for a plethora of viruses. However, the exact role(s) of integrins in viral pathogen internalization has yet to be elaborately described. Notably, several viruses harbor integrin-recognition motifs displayed on viral envelope/capsid-associated proteins. The most common of these motifs is the minimal peptide sequence for binding integrins, RGD (Arg-Gly-Asp), which is known for its role in virus infection via its ability to interact with over half of the more than 20 known integrins. Not all virus-integrin interactions are RGD-dependent, however. Non-RGD-binding integrins have also been shown to effectively promote virus entry and infection as well. Such virus-integrin binding is shown to facilitate adhesion, cytoskeleton rearrangement, integrin activation, and increased intracellular signaling. Also, we have attempted to discuss the role of carbohydrate moieties in virus interactions with receptor-like host cell surface integrins that drive the process of internalization. As much as possible, this article examines the published literature regarding the role of integrins in terms of virus infection and virus-encoded glycosylated proteins that mediate interactions with integrins, and it explores the idea of targeting these receptors as a therapeutic treatment option.