sars4

The small envelope (E) protein (sars4) is found in low abundance in the virion. Recombinantly expressed E protein appears to cause membrane permeability of the host cell in a porin-like fashion. Synthetic E protein was shown to form cation-permeable ion channels in planar lipid bilayers. It was recently shown to induce apoptosis in transfected T cells, which was inhibited by anti-apoptotic protein Bcl-xL. SARS-CoV E protein interacts with Bcl-xL in vitro and in vivo via the BH3 domain of Bcl-xL and a novel BH3-like region located in the C-terminal cytosolic domain of the E protein. These may explain the mechanism behind the T cell apoptosis contributing SARS-CoV-induced lymphopenia observed in most SARS patients. The E protein in coronaviruses functions in viral budding by causing membrane tubulation, and is the only viral protein required for this process. Structurally, it is a helical protein, with a 26-residue almost palindromic transmembrane region which forms a helical hairpin. SARS E protein also contains some hydrophilic residues in the helical region, resembling the influenza virus M2 protein, the best characterized ion-channel forming viroporin with four alpha-helices and a tetrameric quaternary structure. If the E protein forms ion channels in cellular membranes, it would offer another attractive target for anti-SARS strategies.

Liao Y, Lescar J, Tam JP, Liu DX (2004) Expression of SARS coronavirus envelope protein in Escherichia coli cells alters membrane permeability. Biochem. Biophys. Res. Commun. 325: 374--380.

Lai CW, Chung YC, Lai YK, Chang MD, Hu YC. Expression and Purification of N and E Proteins from Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus: a Comparative Study. Biotechnol Lett. 2005 Jul;27(13):883-91.

Wilson L, McKinlay C, Gage P, Ewart G. SARS coronavirus E protein forms cation-selective ion channels. Virology. 2004 Dec 5;330(1):322-31.

Yang Y, Xiong Z, Zhang S, Yan Y, Nguyen J, Ng B, Lu H, Brendese J, Yang F, Wang H, Yang XF. Bcl-xL inhibits T cell apotosis induced by expression of SARS coronavirus E protein in the absence of growth factors. Biochem J. 2005 Jul 28;

H. Vennema, G.J. Godeke, J.W. Rossen, W.F. Voorhout, M.C. Horzinek, D.J. Opstelten and P.J. Rottier, Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes. EMBO J. 15 (1996), pp. 2020–2028.

Arbely E, Khattari Z, Brotons G, Akkawi M, Salditt T, Arkin IT. A highly unusual palindromic transmembrane helical hairpin formed by SARS coronavirus E protein. J Mol Biol. 2004 Aug 13;341(3):769-79.

Liao Y, Lescar J, Tam JP, Liu DX. Expression of SARS-coronavirus envelope protein in Escherichia coli cells alters membrane permeability. Biochem Biophys Res Commun. 2004 Dec 3;325(1):374-80.