Tetherin inhibits HIV-1 release by directly tethering virions to cells.
Publication/Presentation Date
10-30-2009
Abstract
Tetherin is an interferon-induced protein whose expression blocks the release of HIV-1 and other enveloped viral particles. The underlying mechanism by which tetherin functions and whether it directly or indirectly causes virion retention are unknown. Here, we elucidate the mechanism by which tetherin exerts its antiviral activity. We demonstrate, through mutational analyses and domain replacement experiments, that tetherin configuration rather than primary sequence is critical for antiviral activity. These findings allowed the design of a completely artificial protein, lacking sequence homology with native tetherin, that nevertheless mimicked its antiviral activity. We further show that tetherin is incorporated into HIV-1 particles as a parallel homodimer using either of its two membrane anchors. These results indicate that tetherin functions autonomously and directly and that infiltration of virion envelopes by one or both of tetherin's membrane anchors is necessary, and likely sufficient, to tether enveloped virus particles that bud through the plasma membrane.
Volume
139
Issue
3
First Page
499
Last Page
511
ISSN
1097-4172
Published In/Presented At
Perez-Caballero, D., Zang, T., Ebrahimi, A., McNatt, M. W., Gregory, D. A., Johnson, M. C., & Bieniasz, P. D. (2009). Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell, 139(3), 499–511. https://doi.org/10.1016/j.cell.2009.08.039
Disciplines
Medicine and Health Sciences
PubMedID
19879838
Department(s)
Department of Emergency Medicine
Document Type
Article