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).

This family belongs to the Viroporin-1.



Chacko, N., N.N. Mohanty, S.K. Biswas, K. Chand, R. Yogisharadhya, A.B. Pandey, B. Mondal, and S.B. Shivachandra. (2015). A coiled-coil motif in non-structural protein 3 (NS3) of bluetongue virus forms an oligomer. Virus Genes 51: 244-251.

Han, Z. and R.N. Harty. (2004). The NS3 protein of bluetongue virus exhibits viroporin-like properties. J. Biol. Chem. 279: 43092-43097.


TC#NameOrganismal TypeExample

Viroporin, NS3, of 229 aas and 2 TMSs (Han and Harty 2004) with N-terminal coiled-coil domains that may promote oligomeric pore formation (Chacko et al. 2015).

NS3 of BlueTongue Virus


NS3 of 217 aas and 2 TMSs.

NS3 of African horse sickness virus


NS3 of 264 aas and 2 TMSs.

NS3 of Umatilla virus


Non-structural protein, NS3 or Nsp3, of 251 aas and 2 TMSs.

Nsp3 of Mobuck virus


TC#NameOrganismal TypeExample

NS3 of 171 aas and 2 TMSs.

NS3 of Great Island virus