Innate sensing of HIV-1 assembly by Tetherin induces NFκB-dependent proinflammatory responses. - Archive ouverte HAL Access content directly
Journal Articles Cell Host and Microbe Year : 2012

Innate sensing of HIV-1 assembly by Tetherin induces NFκB-dependent proinflammatory responses.

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Abstract

Antiviral proteins that recognize pathogen-specific or aberrantly located molecular motifs are perfectly positioned to act as pattern-recognition receptors and signal to the immune system. Here we investigated whether the interferon-induced viral restriction factor tetherin (CD317/BST2), which is known to inhibit HIV-1 particle release by physically tethering virions to the cell surface, has such a signaling role. We find that upon restriction of Vpu-defective HIV-1, tetherin acts as a virus sensor to induce NFκB-dependent proinflammatory gene expression. Signaling requires both tetherin's extracellular domain involved in virion retention and determinants in the cytoplasmic tail, including an endocytic motif, although signaling is independent of virion endocytosis. Furthermore, recruitment of the TNF-receptor-associated factor TRAF6 and activation of the mitogen-activated protein kinase TAK1 are critical for signaling. Human tetherin's ability to mediate efficient signaling may have arisen as a result of a five amino acid deletion that occurred in hominids after their divergence from chimpanzees.

Dates and versions

hal-01121777 , version 1 (02-03-2015)

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Rui Pedro Galão, Anna Le Tortorec, Suzanne Pickering, Tonya Kueck, Stuart J D Neil. Innate sensing of HIV-1 assembly by Tetherin induces NFκB-dependent proinflammatory responses.. Cell Host and Microbe, 2012, 12 (5), pp.633-44. ⟨10.1016/j.chom.2012.10.007⟩. ⟨hal-01121777⟩
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