1.A.68 The Viral Small Hydrophobic Viroporin (V-SH) Family

The small hydrophobic (SH) protein from the human respiratory syncytial virus (hRSV) is a glycoprotein of 64 amino acids with one putative TMS and channel activity. Although SH proteins are important for viral infectivity, their exact roles during viral infection are not clear. Gan et al., 2008 studied the secondary structure, orientation, and oligomerization of the transmembrane domain of SH (SH-TM) in the presence of lipid bilayers. Only one oligomer, a pentamer, was observed. 

Conductance studies of SH-TM demonstrated ion channel activity which is cation selective and inactive below the predicted pK(a) of histidine. Thus, the transmembrane domain of the SH protein forms pentameric alpha-helical bundles that form cation-selective ion channels in planar lipid bilayers. Gan et al., 2008 suggest a model for this pore.

The absence of the small hydrophobic (SH) protein encoded by the human respiratory syncytial virus (hRSV) leads to viral attenuation and prevents apoptosis in infected cells. Gan et al. (2012) examined the structure of the SH protein in detergent micelles and in lipid bilayers. In detergent micelles, the TM domain is flanked N-terminally by a α-helix that forms a ring around the lumen of the pore, and C-terminally by an extended β-turn. The SH protein was found in the plasma membrane of transiently expressing HEK293 cells, which showed pH-dependent (acid-activated) channel activity. Channel activity was abolished in mutants lacking both native His residues, H22 and H51, but not when either His was present. Gan et al. (2012) proposed that the pentameric SH protein is a physiologically relevant conformation, albeit probably not the only one, in which SH contributes to RSV infection and replication.

The generalized reaction catalyzed by V-SHP is:

ions (in) ⇌ ions (out)