PMID- 34883114
OWN - NLM
STAT- MEDLINE
DCOM- 20220509
LR  - 20220531
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Linking)
VI  - 434
IP  - 6
DP  - 2022 Mar 30
TI  - Virus-stimulated Dendritic Cells Elicit a T Antiviral Transcriptional Signature 
      in Human CD4+ Lymphocytes.
PG  - 167389
LID - S0022-2836(21)00626-4 [pii]
LID - 10.1016/j.jmb.2021.167389 [doi]
AB  - Dendritic cells (DCs) play a pivotal role in the functional differentiation of 
      CD4+ T cells in response to pathogens. In CD4+ T cells, HIV-1 replicates 
      efficiently, while HIV-2, a related virus of reduced pathogenicity, is better 
      controlled. How the DC response to HIV-1 vs HIV-2 contributes to programming an 
      antiviral state in CD4+ T cells is not known. Here, we identify a transcriptional 
      signature associated with progressive resistance to HIV infection in CD4+ T 
      cells. We developed a model of naive CD4+ T cell priming by DCs stimulated with a 
      panel of seven viruses or synthetic ligands for the viral nucleic acid sensors 
      cGAS and TLRs. DCs produced a cytokine response to HIV-2 infection more similar 
      to the response to cGAS ligands than TLR ligands. In response to these signals, 
      naive CD4+ T cells acquired a gradual antiviral resistance to subsequent HIV 
      infection. The antiviral state was concomitant with the induction of the T(H1) 
      cytokine IFNgamma and the type I interferon-stimulated gene (ISG) MX1, while the 
      T(FH) cytokine IL-21 was not increased. By performing a transcriptional network 
      analysis in T cells, we identified five distinct gene modules with characteristic 
      ISG, T(H1), T(FH), IFN-I and proliferative signatures. Finally, we leverage this 
      module to assemble a T antiviral signature of 404 genes that correlate with the 
      antiviral state in T cells. Altogether, the study illuminates the programming of 
      the antiviral state in T cells. The T antiviral gene signature in human CD4+ 
      lymphocytes constitutes a resource for genetic screens and genomics analysis.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Cerboni, Silvia
AU  - Cerboni S
AD  - Institut Curie, PSL Research University, INSERM U932, Paris, France.
FAU - Marques-Ladeira, Santy
AU  - Marques-Ladeira S
AD  - Institut Curie, PSL Research University, INSERM U932, Paris, France.
FAU - Manel, Nicolas
AU  - Manel N
AD  - Institut Curie, PSL Research University, INSERM U932, Paris, France. Electronic 
      address: Nicolas.manel@curie.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211206
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Cytokines)
RN  - 0 (Ligands)
RN  - EC 2.7.7.- (Nucleotidyltransferases)
SB  - IM
MH  - *CD4-Positive T-Lymphocytes/immunology
MH  - Cytokines/metabolism
MH  - *Dendritic Cells/immunology/virology
MH  - *HIV Infections/genetics/immunology
MH  - *HIV-2/genetics/physiology
MH  - Humans
MH  - Ligands
MH  - Nucleotidyltransferases/metabolism
MH  - *Transcriptome
MH  - Virus Replication
OTO - NOTNLM
OT  - CD4+ T cells
OT  - HIV
OT  - antiviral state
OT  - dendritic cells
OT  - gene signature
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/12/10 06:00
MHDA- 2022/05/10 06:00
CRDT- 2021/12/09 20:13
PHST- 2021/09/24 00:00 [received]
PHST- 2021/11/25 00:00 [revised]
PHST- 2021/11/29 00:00 [accepted]
PHST- 2021/12/10 06:00 [pubmed]
PHST- 2022/05/10 06:00 [medline]
PHST- 2021/12/09 20:13 [entrez]
AID - S0022-2836(21)00626-4 [pii]
AID - 10.1016/j.jmb.2021.167389 [doi]
PST - ppublish
SO  - J Mol Biol. 2022 Mar 30;434(6):167389. doi: 10.1016/j.jmb.2021.167389. Epub 2021 
      Dec 6.