Towers, GJ;
Khan, H;
Sumner, RP;
Rasaiyaah, J;
Tan, CP;
Rodriguez Plata, MT;
Van Tulleken, C;
... Milne, RSB; + view all
(2020)
HIV-1 Vpr antagonizes innate immune activation by targeting karyopherin-mediated NF- κB/IRF3 nuclear transport.
eLife
, 9
, Article e60821. 10.7554/eLife.60821.
(In press).
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Abstract
HIV-1 must replicate in cells that are equipped to defend themselves from infection through intracellular innate immune systems. HIV-1 evades innate immune sensing through encapsidated DNA synthesis and encodes accessory genes that antagonize specific antiviral effectors. Here we show that both particle associated, and expressed HIV-1 Vpr, antagonize the stimulatory effect of a variety of pathogen associated molecular patterns by inhibiting IRF3 and NF-κB nuclear transport. Phosphorylation of IRF3 at S396, but not S386, was also inhibited. We propose that, rather than promoting HIV-1 nuclear import, Vpr interacts with karyopherins to disturb their import of IRF3 and NF-κB to promote replication in macrophages. Concordantly, we demonstrate Vpr dependent rescue of HIV-1 replication in human macrophages from inhibition by cGAMP, the product of activated cGAS. We propose a model that unifies Vpr manipulation of nuclear import and inhibition of innate immune activation to promote HIV-1 replication and transmission.
| Type: | Article |
|---|---|
| Title: | HIV-1 Vpr antagonizes innate immune activation by targeting karyopherin-mediated NF- κB/IRF3 nuclear transport |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.60821 |
| Publisher version: | https://doi.org/10.7554/eLife.60821 |
| Language: | English |
| Additional information: | Copyright © 2020, Khan et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) permitting unrestricted use and redistribution provided that the original author and source are credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10117687 |
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