Upregulation of BST-2 by Type I Interferons Reduces the Capacity of Vpu To Protect HIV-1-Infected Cells from NK Cell Responses.
Antigens, CD
/ genetics
CD4-Positive T-Lymphocytes
/ immunology
Down-Regulation
GPI-Linked Proteins
/ genetics
HEK293 Cells
HIV Infections
/ immunology
HIV-1
Human Immunodeficiency Virus Proteins
/ genetics
Humans
Immune Evasion
Interferon Type I
/ pharmacology
Killer Cells, Natural
/ immunology
Receptors, Virus
/ genetics
Signaling Lymphocytic Activation Molecule Family
/ genetics
Transcriptional Activation
Up-Regulation
Viral Regulatory and Accessory Proteins
/ genetics
ADCC
DNAM-1
HIV
NK cells
NTB-A
PVR
Vpu
type I IFNs
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
18 06 2019
18 06 2019
Historique:
entrez:
20
6
2019
pubmed:
20
6
2019
medline:
12
2
2020
Statut:
epublish
Résumé
The HIV-1 accessory protein Vpu enhances viral release by counteracting the restriction factor BST-2. Furthermore, Vpu promotes NK cell evasion by downmodulating cell surface NTB-A and PVR, known ligands of the NK cell receptors NTB-A and DNAM-1, respectively. While it has been established that Vpu's transmembrane domain (TMD) is required for the interaction and intracellular sequestration of BST-2, NTB-A, and PVR, it remains unclear how Vpu manages to target these proteins simultaneously. In this study, we show that upon upregulation, BST-2 is preferentially downregulated by Vpu over its other TMD substrates. We found that type I interferon (IFN)-mediated BST-2 upregulation greatly impairs the ability of Vpu to downregulate NTB-A and PVR. Our results suggest that occupation of Vpu by BST-2 affects its ability to downregulate other TMD substrates. Accordingly, knockdown of BST-2 increases Vpu's potency to downmodulate NTB-A and PVR in the presence of type I IFN treatment. Moreover, we show that expression of human BST-2, but not that of the macaque orthologue, decreases Vpu's capacity to downregulate NTB-A. Importantly, we show that type I IFNs efficiently sensitize HIV-1-infected cells to NTB-A- and DNAM-1-mediated direct and antibody-dependent NK cell responses. Altogether, our results reveal that type I IFNs decrease Vpu's polyfunctionality, thus reducing its capacity to protect HIV-1-infected cells from NK cell responses.
Identifiants
pubmed: 31213558
pii: mBio.01113-19
doi: 10.1128/mBio.01113-19
pmc: PMC6581860
pii:
doi:
Substances chimiques
Antigens, CD
0
BST2 protein, human
0
GPI-Linked Proteins
0
Human Immunodeficiency Virus Proteins
0
Interferon Type I
0
Receptors, Virus
0
SLAMF6 protein, human
0
Signaling Lymphocytic Activation Molecule Family
0
Viral Regulatory and Accessory Proteins
0
poliovirus receptor
0
vpu protein, Human immunodeficiency virus 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI126620
Pays : United States
Organisme : Medical Research Council
ID : G0801937
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI114266
Pays : United States
Organisme : CIHR
Pays : Canada
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : UM1 AI144371
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111789
Pays : United States
Informations de copyright
Copyright © 2019 Prévost et al.
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