Cutting edge: paradoxical roles of BST2/tetherin in promoting type I IFN response and viral infection

• Published in: The Journal of immunology (1950) 2012-03, Vol.188 (6), p.2488-2492
• Main Authors: Swiecki, Melissa, Wang, Yaming, Gilfillan, Susan, Lenschow, Deborah J, Colonna, Marco
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - immunology; Antigens, CD - metabolism; Cell Separation; Flow Cytometry; Interferon Type I - immunology; Interferon Type I - metabolism; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice; Mice, Knockout; Vesicular stomatitis virus; Virus Diseases - immunology; Virus Diseases - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1103145

Bone marrow stromal Ag 2 (BST2) is a transmembrane protein that prevents virus release from infected cells. It was also reported that BST2 inhibits type I IFN production by plasmacytoid dendritic cells. To determine BST2 impact on antiviral responses in vivo, we generated BST2(-/-) mice. Following infection with a murine retrovirus, BST2(-/-) mice had slightly elevated viral loads; however, infection with other enveloped viruses revealed unexpected roles of BST2. BST2(-/-) mice showed reduced type I IFN production by plasmacytoid dendritic cells. Moreover, BST2(-/-) mice had lower viral titers in lungs following intranasal infection with vesicular stomatitis virus expressing OVA and influenza B and increased numbers of virus-specific CD8 T cells in the lungs, suggesting that BST2 may facilitate entry and/or replication of enveloped viruses and modulate priming of CD8 T cells. These findings suggest complex roles of BST2 beyond retroviral control in vivo, possibly reflecting the involvement of BST2 in endocytosis and intracellular trafficking of viruses, viral nucleic acids, and Ags.