1.A.93 The Bluetongue Virus Non-Structural Protein 3 Viroporin (NS3) Family
NS3 possesses properties commonly associated with viroporins. Han and Harty 2004 reported that: (i) NS3 localizes to the Golgi apparatus and plasma membrane, (ii) NS3 can homo-oligomerize in transfected cells, (iii) targeting of NS3 to the Golgi apparatus and plasma membrane correlates with the enhanced permeability of cells to the translation inhibitor hygromycin B (hyg-B), (iv) amino acids 118-148 comprising TMS1 of NS3 are critical for Golgi targeting and hyg-B permeability, and (v) deletion of amino acids 156-181 comprising transmembrane region 2 (TM2) of NS3 has little to no affect on Golgi targeting and hyg-B permeability. These viroporin-like properties may contribute to the role of NS3 in virus release and may have important implications for pathogenicity of bluetongue virus infections.
Bluetongue, an arthropod-borne non-contagious hemorrhagic disease of small ruminants, is caused by bluetongue virus (BTV). Several structural and non-structural proteins encoded by BTV have been associated with virulence mechanisms. The NS3 proteins have at least three coiled-coil motifs (CCMs). A conserved α-helical heptad sequence was identified at 14-26 aa (CCM-I), 185-198aa (CCM-II), and 94-116 aa (CCM-III). The N-terminus of NS3 (Residues 1 - 117) forms SDS-resistant dimers and high-order oligomers (hexamer and/or octamer). Coiled-coil motifs may be critical for NS protein oligomerization and have potential roles in the formation of viroporin ring/pores with either six or eight subunits (Chacko et al. 2015).