Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway.
Adult
Aged
CD4-Positive T-Lymphocytes
/ drug effects
Dendritic Cells
/ immunology
Female
HIV Infections
/ drug therapy
HIV-1
/ drug effects
Humans
Lymphocyte Activation
/ immunology
Male
Middle Aged
Models, Biological
NF-kappa B
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Phosphorylation
Protein Binding
Proto-Oncogene Proteins c-akt
/ metabolism
Proto-Oncogene Proteins c-fos
/ chemistry
Proto-Oncogene Proteins c-jun
/ chemistry
Receptors, Antigen, T-Cell
/ metabolism
Signal Transduction
TOR Serine-Threonine Kinases
/ metabolism
Virus Latency
/ immunology
Activated T cells
Akt
Dendritic cells
Latency
PI3K
mTOR
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
04
10
2018
revised:
01
02
2019
accepted:
06
02
2019
pubmed:
3
3
2019
medline:
21
8
2019
entrez:
3
3
2019
Statut:
ppublish
Résumé
The latent HIV-1 reservoir in treated patients primarily consists of resting memory CD4 Primary HIV-1 infected cells were used in a latency assay with or without dendritic cells (DCs) and reversion of HIV-1 latency was determined, in the presence or absence of specific pathway inhibitors. Renewed TCR-stimulation or subsequent activation with latency reversing agents (LRAs) did not overcome latency. However, interaction of infected effector cells with DCs triggered further activation of latent HIV-1. When compared to TCR-stimulation only, CD4 This insight could facilitate the development of a novel class of potent LRAs that purge latent HIV beyond levels reached by T-cell activation.
Sections du résumé
BACKGROUND
BACKGROUND
The latent HIV-1 reservoir in treated patients primarily consists of resting memory CD4
METHODS
METHODS
Primary HIV-1 infected cells were used in a latency assay with or without dendritic cells (DCs) and reversion of HIV-1 latency was determined, in the presence or absence of specific pathway inhibitors.
FINDINGS
RESULTS
Renewed TCR-stimulation or subsequent activation with latency reversing agents (LRAs) did not overcome latency. However, interaction of infected effector cells with DCs triggered further activation of latent HIV-1. When compared to TCR-stimulation only, CD4
INTERPRETATION
CONCLUSIONS
This insight could facilitate the development of a novel class of potent LRAs that purge latent HIV beyond levels reached by T-cell activation.
Identifiants
pubmed: 30824386
pii: S2352-3964(19)30086-6
doi: 10.1016/j.ebiom.2019.02.014
pmc: PMC6491380
pii:
doi:
Substances chimiques
NF-kappa B
0
Proto-Oncogene Proteins c-fos
0
Proto-Oncogene Proteins c-jun
0
Receptors, Antigen, T-Cell
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Pagination
97-108Informations de copyright
Copyright © 2019. Published by Elsevier B.V.
Références
Immunology. 1999 Apr;96(4):524-8
pubmed: 10233737
N Engl J Med. 1999 May 27;340(21):1605-13
pubmed: 10341272
AIDS. 1999 Dec 3;13(17):2405-10
pubmed: 10597782
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3394-9
pubmed: 10716728
Blood. 2001 Oct 15;98(8):2574-6
pubmed: 11588058
J Immunol. 2002 Dec 15;169(12):6691-5
pubmed: 12471100
Nat Rev Cancer. 2003 Jan;3(1):11-22
pubmed: 12509763
Mol Cell Biol. 2003 Sep;23(18):6618-30
pubmed: 12944487
FEBS Lett. 2004 Jul 30;571(1-3):50-4
pubmed: 15280016
J Virol. 2005 Feb;79(3):1975-80
pubmed: 15650227
Nat Rev Mol Cell Biol. 2005 Oct;6(10):801-11
pubmed: 16314869
J Clin Microbiol. 1990 Mar;28(3):495-503
pubmed: 1691208
Nat Med. 2007 Oct;13(10):1241-7
pubmed: 17906637
J Virol. 2008 Aug;82(16):7886-96
pubmed: 18524826
Nat Protoc. 2008;3(7):1240-8
pubmed: 18600229
J Virol. 2009 Oct;83(19):9911-22
pubmed: 19605489
Nat Rev Cancer. 2010 May;10(5):342-52
pubmed: 20414202
Trends Biochem Sci. 2011 Jun;36(6):320-8
pubmed: 21531565
Retrovirology. 2011 Jul 20;8:61
pubmed: 21771347
J Immunol. 2011 Nov 1;187(9):4676-85
pubmed: 21957147
Nature. 2012 Jul 25;487(7408):482-5
pubmed: 22837004
J Infect Dis. 2012 Nov;206(9):1443-52
pubmed: 22927449
Virology. 2013 Jan 20;435(2):329-40
pubmed: 23158102
PLoS Pathog. 2013 Mar;9(3):e1003259
pubmed: 23555263
Immunity. 2013 Jul 25;39(1):38-48
pubmed: 23890062
Clin Infect Dis. 2014 Mar;58(6):883-90
pubmed: 24336828
Nat Med. 2014 Apr;20(4):425-9
pubmed: 24658076
Eur J Immunol. 2014 Jul;44(7):1967-75
pubmed: 24723389
Lancet. 1989 Aug 19;2(8660):443-4
pubmed: 2474733
Proc Natl Acad Sci U S A. 2014 May 13;111(19):6860-1
pubmed: 24799684
Lancet. 1989 Jul 22;2(8656):227
pubmed: 2568561
AIDS. 2015 Jun 1;29(9):1003-14
pubmed: 25768834
J Clin Invest. 2015 May;125(5):1901-12
pubmed: 25822022
PLoS Pathog. 2015 Jun 11;11(6):e1004955
pubmed: 26067822
PLoS Pathog. 2015 Jul 30;11(7):e1005063
pubmed: 26225566
J Immunol. 2015 Oct 15;195(8):3759-68
pubmed: 26355155
PLoS Pathog. 2015 Sep 17;11(9):e1005142
pubmed: 26379282
Lancet HIV. 2014 Oct;1(1):e13-21
pubmed: 26423811
Front Immunol. 2016 Jan 11;6:653
pubmed: 26793193
Nature. 2016 Feb 4;530(7588):51-56
pubmed: 26814962
AIDS. 2016 Jun 1;30(9):1385-92
pubmed: 26891037
Nat Med. 2016 Sep;22(9):1043-9
pubmed: 27500724
Cell Host Microbe. 2016 Dec 14;20(6):785-797
pubmed: 27978436
J Clin Invest. 2017 Feb 1;127(2):651-656
pubmed: 28094770
Sci Rep. 2017 Feb 24;7:43231
pubmed: 28233807
J Exp Med. 2017 Apr 3;214(4):959-972
pubmed: 28341641
Nat Med. 2017 Jul;23(7):885-889
pubmed: 28553933
Virulence. 2017 Nov 17;8(8):1732-1743
pubmed: 28762863
Curr Top Microbiol Immunol. 2018;417:1-22
pubmed: 29071474
Sci Transl Med. 2018 Feb 28;10(430):
pubmed: 29491188
Nature. 1995 Jan 12;373(6510):117-22
pubmed: 7529365
Science. 1996 Mar 15;271(5255):1582-6
pubmed: 8599114
J Biol Chem. 1997 Jan 31;272(5):2595-8
pubmed: 9006891
J Virol. 1997 Mar;71(3):2233-40
pubmed: 9032358
Science. 1997 Dec 19;278(5346):2075-80
pubmed: 9405336