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Article

The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin

MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK
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Received: 10 February 2020 / Revised: 15 April 2020 / Accepted: 15 April 2020 / Published: 18 April 2020
(This article belongs to the Special Issue Role of Myeloid Cells in Viral Infections)
Bone Marrow Stromal Cell Antigen 2 (BST-2)/tetherin inhibits the release of numerous enveloped viruses by physically tethering nascent particles to infected cells during the process of viral budding from the cell surface. Tetherin also restricts human immunodeficiency virus (HIV), and pandemic main (M) group HIV type 1s (HIV-1s) are thought to rely exclusively on their Vpu proteins to overcome tetherin-mediated restriction of virus release. However, at least one M group HIV-1 strain, the macrophage-tropic primary AD8 isolate, is unable to express Vpu due to a mutation in its translation initiation codon. Here, using primary monocyte-derived macrophages (MDMs), we show that AD8 Nef protein can compensate for the absence of Vpu and restore virus release to wild type levels. We demonstrate that HIV-1 AD8 Nef reduces endogenous cell surface tetherin levels, physically separating it from the site of viral budding, thus preventing HIV retention. Mechanistically, AD8 Nef enhances internalisation of the long isoform of human tetherin, leading to perinuclear accumulation of the restriction factor. Finally, we show that Nef proteins from other HIV strains also display varying degrees of tetherin antagonism. Overall, we show that M group HIV-1s can use an accessory protein other than Vpu to antagonise human tetherin. View Full-Text
Keywords: BST-2; HIV-1; Nef; tetherin; macrophages; PBMC BST-2; HIV-1; Nef; tetherin; macrophages; PBMC
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MDPI and ACS Style

Giese, S.; Lawrence, S.P.; Mazzon, M.; Nijmeijer, B.M.; Marsh, M. The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin. Viruses 2020, 12, 459. https://0-doi-org.brum.beds.ac.uk/10.3390/v12040459

AMA Style

Giese S, Lawrence SP, Mazzon M, Nijmeijer BM, Marsh M. The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin. Viruses. 2020; 12(4):459. https://0-doi-org.brum.beds.ac.uk/10.3390/v12040459

Chicago/Turabian Style

Giese, Sebastian, Scott P. Lawrence, Michela Mazzon, Bernadien M. Nijmeijer, and Mark Marsh. 2020. "The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin" Viruses 12, no. 4: 459. https://0-doi-org.brum.beds.ac.uk/10.3390/v12040459

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