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Viruses 2015, 7(4), 2147-2167;

BST2/Tetherin Inhibition of Alphavirus Exit

Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA
Current address: Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild Science Building, 299 Campus Drive, Stanford, CA 94305, USA.
Current address: Centre INRS-Institut Armand-Frappier, 531, boulevard des Prairies, Laval, QC H7V 1B7, Canada.
Author to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 13 March 2015 / Revised: 8 April 2015 / Accepted: 17 April 2015 / Published: 22 April 2015
(This article belongs to the Section Animal Viruses)
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Alphaviruses such as chikungunya virus (CHIKV) and Semliki Forest virus (SFV) are small enveloped RNA viruses that bud from the plasma membrane. Tetherin/BST2 is an interferon-induced host membrane protein that inhibits the release of many enveloped viruses via direct tethering of budded particles to the cell surface. Alphaviruses have highly organized structures and exclude host membrane proteins from the site of budding, suggesting that their release might be insensitive to tetherin inhibition. Here, we demonstrated that exogenously-expressed tetherin efficiently inhibited the release of SFV and CHIKV particles from host cells without affecting virus entry and infection. Alphavirus release was also inhibited by the endogenous levels of tetherin in HeLa cells. While rubella virus (RuV) and dengue virus (DENV) have structural similarities to alphaviruses, tetherin inhibited the release of RuV but not DENV. We found that two recently identified tetherin isoforms differing in length at the N-terminus exhibited distinct capabilities in restricting alphavirus release. SFV exit was efficiently inhibited by the long isoform but not the short isoform of tetherin, while both isoforms inhibited vesicular stomatitis virus exit. Thus, in spite of the organized structure of the virus particle, tetherin specifically blocks alphavirus release and shows an interesting isoform requirement. View Full-Text
Keywords: alphavirus; tetherin/BST2; virus budding; rubella virus; dengue virus alphavirus; tetherin/BST2; virus budding; rubella virus; dengue virus

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Ooi, Y.S.; Dubé, M.; Kielian, M. BST2/Tetherin Inhibition of Alphavirus Exit. Viruses 2015, 7, 2147-2167.

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