Friday, October 3, 2008

Coronavirus Envelope Protein Promotes Assembly and Release of Virus

Coronaviruses assemble at membranes of the endoplasmic reticulum intermediate compartment (ERGIC) where viral proteins accumulate and virions bud into the lumen before transport through the exocytic pathway for release from cells. The small viral envelope (E) proteins clearly play important, but yet not fully understood roles in enhancing coronavirus assembly and release. The proteins are fairly divergent, but the overall hydrophobic nature and some residues are conserved across the family. The proteins also exhibit ion channel/viroporin activity. Recent reverse genetic studies from our lab identified three regions within MHV A59 E, the hydrophobic domain and conserved residues, cysteines and prolines, as important contributors for its function(s). Insertion mutagenesis and residue substitutions demonstrate that the predicted transmembrane (TM) alpha-helical structure and polar hydrophilic residues are necessary for wild-type function of the protein. Ongoing studies are providing insight about ion channel activity of the mutant proteins in lipid bilayers and if/how these correlate with phenotypes of E mutant viruses. From these studies we propose a model for how the E protein functions through interactions with the host cell and possibly the membrane protein to enhance both virus assembly and release.