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J. Biol. Chem., Vol. 279, Issue 41, 43092-43097, October 8, 2004
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From the Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6049
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 118148 comprising transmembrane region 1 (TM1) of NS3 are critical for Golgi targeting and hyg-B permeability, and (v) deletion of amino acids 156181 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.
Received for publication, April 2, 2004 , and in revised form, July 2, 2004.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA 19104-6049. Tel.: 215-573-4485; Fax: 215-898-7887; E-mail: rharty{at}vet.upenn.edu.
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