title: Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin.
abstract: The expression of many putative antiviral genes is upregulated when cells encounter type I interferon (IFN), but the actual mechanisms by which many IFN-induced gene products inhibit virus replication are poorly understood. A recently identified IFN-induced antiretroviral protein, termed tetherin (previously known as BST-2 or CD317), blocks the release of nascent human immunodeficiency virus type 1 (HIV-1) particles from infected cells, and an HIV-1 accessory protein, Vpu, acts as a viral antagonist of tetherin. Here, we show that tetherin is capable of blocking not only the release of HIV-1 particles but also the release of particles assembled using the major structural proteins of a variety of prototype retroviruses, including members of the alpharetrovirus, betaretrovirus, deltaretrovirus, lentivirus, and spumaretrovirus families. Moreover, we show that the release of particles assembled using filovirus matrix proteins from Marburg virus and Ebola virus is also sensitive to inhibition by tetherin. These findings indicate that tetherin is a broadly specific inhibitor of enveloped particle release, and therefore, inhibition is unlikely to require specific interactions with viral proteins. Nonetheless, tetherin colocalized with nascent virus-like particles generated by several retroviral and filoviral structural proteins, indicating that it is present at, or recruited to, sites of particle assembly. Overall, tetherin is potentially active against many enveloped viruses and likely to be an important component of the antiviral innate immune defense.
authors.affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York, USA.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Jouvenet
authors.forename: Stuart J D
authors.initials: SJ
authors.lastname: Neil
authors.forename: Maria
authors.initials: M
authors.lastname: Zhadina
authors.forename: Trinity
authors.initials: T
authors.lastname: Zang
authors.forename: Zerina
authors.initials: Z
authors.lastname: Kratovac
authors.forename: Youngnam
authors.initials: Y
authors.lastname: Lee
authors.forename: Matthew
authors.initials: M
authors.lastname: McNatt
authors.forename: Theodora
authors.initials: T
authors.lastname: Hatziioannou
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
mesh_terms: D015703:Antigens, CD / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D016563:Filoviridae / Q000187:drug effects*; D058851:GPI-Linked Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D012190:Retroviridae / Q000187:drug effects*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D000998:Antiviral Agents; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2