The SARS Coronavirus E Protein Interacts with PALS1 and Alters Tight Junction Formation and Epithelial Morphogenesis

Teoh, Kim-Tat; Siu, Yu-Lam; Chan, Wing-Lim; Schlüter, Marc A.; Liu, Chia-Jen; Peiris, J. S. Malik; Bruzzone, Roberto; Margolis, Benjamin; Nal, Béatrice

We have hypothesized that the carboxy-terminal (CT) domain of SARS-CoV structural proteins interact with cytosolic cellular machineries in infected epithelia and that such interactions may be involved in virus-induced pathogenesis. Here we show that the CT of the SARS-CoV envelope protein E binds the human TJ protein PALS1 in human epithelial cells. E is a small hydrophobic integral membrane protein of 76 amino acid residues, which plays a major but not fully understood role in virus morphogenesis and budding (Liu et al., 2007; Siu et al., 2008). In transfected and infected cells, it is known that E localizes at the membranes of the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and Golgi apparatus, where virus assembly occurs (Nal et al., 2005; Liu et al., 2007; Siu et al., 2008). In this report we study the biochemical interaction between SARS-CoV E and human PALS1 and investigate the consequences of E expression in MDCKII epithelial cells on cyst morphogenesis and tight junction formation. We propose a model which places E as a virulent factor that hijacks the TJ-associated protein PALS1, causing severe damage to the epithelial barrier. Our data provide new insight into the molecular mechanisms that contribute to SARS-CoV-induced pathogenesis in infected epithelia.