The actin cytoskeleton as a barrier to virus infection of polarized epithelial cells

Abstract

Many diverse viruses target a polarized epithelial monolayer during host invasion. The polarized epithelium is adept at restricting the movement of solutes, ions, macromolecules, and pathogens across the mucosa. This regulation can be attributed to the presence of a junctional complex between adjacent cells and to an intricate network of actin filaments that provides support to the subapical membrane and stabilizes intercellular junctions. It is therefore not surprising that many viruses have evolved highly varied strategies to dissolve or modulate the cortical actin meshwork to promote infection of polarized cells. In this review, we will discuss the cell biological properties of the actin cytoskeleton in polarized epithelial cells and review the known mechanisms utilized by viral pathogens to manipulate this system in order to facilitate their infection.

Keywords: actin cytoskeleton; polarized epithelium; tight junctions; virus entry.

Figure 1

Model of Polarized Epithelial Cells. (A) Polarized intestinal epithelial cells (IECs) lining the gastrointestinal (GI) tract have distinct apical and basolateral surface domains. The apical domains are intimately associated with the actin cytoskeletal network. Microvilli localize to the apical surface and are anchored by interactions with actin-binding proteins ezrin, radixin, and moesin (ERM). (B) The highlighted area of the apical domain demonstrates the close interactions between actin and junctional complex proteins [ZO-1, ZO-2, ZO-3, Afadin, multi-PDZ domain protein 1 (MUPP1), MAGI, α- and β-catenin].