The NS3 protein of bluetongue virus exhibits viroporin-like properties.
Viroporins compose a group of small hydrophobic transmembrane proteins that can form hydrophilic pores through lipid bilayers. Viroporins have been implicated in promoting virus release from infected cells and in affecting cellular functions including protein trafficking and membrane permeability. Nonstructural protein 3 (NS3) of bluetongue virus has been shown previously to be important for efficient release of newly made virions from infected cells. In this report, we demonstrate that NS3 possesses properties commonly associated with viroporins. Our findings indicate that: (i) NS3 localizes to the Golgi apparatus and plasma membrane in transfected cells, (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 transmembrane region 1 (TM1) 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.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6049, USA.
Ziying
Z
Han
Ronald N
RN
Harty
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D006921:Hygromycin B / Q000737:chemistry; D015151:Immunoblotting; D047468:Immunoprecipitation; D008051:Lipid Bilayers / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010539:Permeability; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism
D000596:Amino Acids; D008051:Lipid Bilayers; D008565:Membrane Proteins; C075080:S10 protein, Bluetongue virus; D017361:Viral Nonstructural Proteins; D006921:Hygromycin B