1.A.65 The Coronavirus Viroporin E Protein (Viroporin E) Family
Viroporins are a growing family of viral proteins able to enhance membrane permeability, promoting virus budding. The viroporin activity of the E protein from murine hepatitis virus (MHV), a member of the coronaviruses, resulted in exit of labeled nucleotides from E. coli cells to the cytoplasm upon expression of MHV E. In addition, enhanced entry of the antibiotic hygromycin B occurred at levels comparable to those observed with the viroporin 6K from Sindbis virus. Mammalian cells are also readily permeabilized by the expression of the MHV E protein. Finally, brefeldin A powerfully blocks the viroporin activity of the E protein in BHK cells, suggesting that an intact vesicular system is necessary for this coronavirus to permeabilize mammalian cells (Madan et al., 2005).
More recently, coronavirus (CoV) envelope (E) protein ion channel activity was determined in channels formed in planar lipid bilayers by peptides representing either the transmembrane domain of severe acute respiratory syndrome CoV (SARS-CoV) E protein, or the full-length E protein. Both of them formed voltage-independent ion-conductive pores with symmetric ion transport properties (Verdiá-Báguena et al., 2012). Mutations N15A and V25F located in the transmembrane domain prevented ion conductivity. E protein derived channels showed no cation preference in non-charged lipid membranes, whereas they behaved as pores with mild cation selectivity in negatively-charged lipid membranes. Thus, the ion conductance was controlled by the lipid composition of the membrane. Lipid charge also regulated the selectivity of a HCoV-229E E protein derived peptide. These results suggested that the lipids are functionally involved in E protein ion channel activity, forming a protein-lipid pore (Verdiá-Báguena et al. 2013).
The generalized reaction catalyzed by the MHV E protein is:
small molecules (out) small molecules (in)