eprintid: 10096542
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/09/65/42
datestamp: 2020-05-01 13:05:56
lastmod: 2021-09-17 22:26:51
status_changed: 2020-05-01 13:05:56
type: article
metadata_visibility: show
creators_name: Giese, S
creators_name: Lawrence, SP
creators_name: Mazzon, M
creators_name: Nijmeijer, BM
creators_name: Marsh, M
title: The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D77
keywords: BST-2, HIV-1, Nef, PBMC, macrophages, tetherin
note: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
abstract: 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.
date: 2020-04-18
date_type: published
official_url: https://doi.org/10.3390/v12040459
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1779102
doi: 10.3390/v12040459
pii: v12040459
lyricists_name: Lawrence, Scott
lyricists_name: Marsh, Mark
lyricists_id: SPLAW85
lyricists_id: MCPMA80
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Viruses
volume: 12
number: 4
article_number: 459
event_location: Switzerland
citation:        Giese, S;    Lawrence, SP;    Mazzon, M;    Nijmeijer, BM;    Marsh, M;      (2020)    The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin.                   Viruses , 12  (4)    , Article 459.  10.3390/v12040459 <https://doi.org/10.3390/v12040459>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10096542/1/viruses-12-00459-v2.pdf