Tetherin inhibits HIV-1 release by directly tethering virions to cells

By D. Pérez-Caballero, Trinity M Zang, Alaleh Ebrahimi, Matthew W. McNatt, D. Gregory, Marc C. Johnson, P. Bieniasz. Cell, 2009

628 citations recorded by the source corpus.

Summary 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 plasma membrane.

Subfields: Epidemiology, Immunology, Virology

View Paper: https://www.semanticscholar.org/paper/892a1a6db85eb3ea8756253afd754275c634a9ef

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Citations in the corpus

• Interferon-Stimulated Genes: A Complex Web of Host Defenses (2014, background): “membrane anchors to trap HIV-1 virions on the plasma membrane (Figure 4) (205).”
• LGP2 is a positive regulator of RIG-I– and MDA5-mediated antiviral responses (2010, background): “The importance of the spacer function is documented by our mutagenesis studies of the coiled-coil region and by the deletion of the coiled coil (Perez-Caballero et al., 2009), both of which lead to a loss of the HIV-1 retention function.”