PMID- 32038656
OWN - NLM
STAT- MEDLINE
DCOM- 20210219
LR  - 20210219
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Synthetic Abortive HIV-1 RNAs Induce Potent Antiviral Immunity.
PG  - 8
LID - 10.3389/fimmu.2020.00008 [doi]
LID - 8
AB  - Strong innate and adaptive immune responses are paramount in combating viral 
      infections. Dendritic cells (DCs) detect viral infections via cytosolic RIG-I 
      like receptors (RLRs) RIG-I and MDA5 leading to MAVS-induced immunity. The 
      DEAD-box RNA helicase DDX3 senses abortive human immunodeficiency virus 1 (HIV-1) 
      transcripts and induces MAVS-dependent type I interferon (IFN) responses, 
      suggesting that abortive HIV-1 RNA transcripts induce antiviral immunity. Little 
      is known about the induction of antiviral immunity by DDX3-ligand abortive HIV-1 
      RNA. Here we synthesized a 58 nucleotide-long capped RNA (HIV-1 Cap-RNA(58)) that 
      mimics abortive HIV-1 RNA transcripts. HIV-1 Cap-RNA(58) induced potent type I 
      IFN responses in monocyte-derived DCs, monocytes, macrophages and primary CD1c(+) 
      DCs. Compared with RLR agonist poly-I:C, HIV-1 Cap-RNA(58) induced comparable 
      levels of type I IFN responses, identifying HIV-1 Cap-RNA(58) as a potent trigger 
      of antiviral immunity. In monocyte-derived DCs, HIV-1 Cap-RNA(58) activated the 
      transcription factors IRF3 and NF-kappaB. Moreover, HIV-1 Cap-RNA(58) induced DC 
      maturation and the expression of pro-inflammatory cytokines. HIV-1 
      Cap-RNA(58)-stimulated DCs induced proliferation of CD4(+) and CD8(+) T cells and 
      differentiated naive T helper (T(H)) cells toward a T(H)2 phenotype. Importantly, 
      treatment of DCs with HIV-1 Cap-RNA(58) resulted in an efficient antiviral innate 
      immune response that reduced ongoing HIV-1 replication in DCs. Our data strongly 
      suggest that HIV-1 Cap-RNA(58) induces potent innate and adaptive immune 
      responses, making it an interesting addition in vaccine design strategies.
CI  - Copyright (c) 2020 Stunnenberg, Sprokholt, van Hamme, Kaptein, Zijlstra-Willems, 
      Gringhuis and Geijtenbeek.
FAU - Stunnenberg, Melissa
AU  - Stunnenberg M
AD  - Department of Experimental Immunology, Amsterdam Infection and Immunity 
      Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
FAU - Sprokholt, Joris K
AU  - Sprokholt JK
AD  - Department of Experimental Immunology, Amsterdam Infection and Immunity 
      Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
FAU - van Hamme, John L
AU  - van Hamme JL
AD  - Department of Experimental Immunology, Amsterdam Infection and Immunity 
      Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
FAU - Kaptein, Tanja M
AU  - Kaptein TM
AD  - Department of Experimental Immunology, Amsterdam Infection and Immunity 
      Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
FAU - Zijlstra-Willems, Esther M
AU  - Zijlstra-Willems EM
AD  - Department of Experimental Immunology, Amsterdam Infection and Immunity 
      Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
FAU - Gringhuis, Sonja I
AU  - Gringhuis SI
AD  - Department of Experimental Immunology, Amsterdam Infection and Immunity 
      Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
FAU - Geijtenbeek, Teunis B H
AU  - Geijtenbeek TBH
AD  - Department of Experimental Immunology, Amsterdam Infection and Immunity 
      Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200123
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (IRF3 protein, human)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Interferon Type I)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - *Adaptive Immunity
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Dendritic Cells/immunology/virology
MH  - HIV Infections/*immunology/virology
MH  - HIV-1/*genetics
MH  - Host Microbial Interactions/*immunology
MH  - Humans
MH  - *Immunity, Innate
MH  - Interferon Regulatory Factor-3/metabolism
MH  - Interferon Type I/metabolism
MH  - Macrophages/immunology/virology
MH  - Monocytes/immunology/virology
MH  - NF-kappa B/metabolism
MH  - RNA, Viral/chemical synthesis/immunology/*pharmacology
MH  - Signal Transduction/drug effects
MH  - T-Lymphocytes/drug effects/immunology
MH  - Transcription, Genetic
PMC - PMC6990453
OTO - NOTNLM
OT  - DDX3
OT  - abortive HIV-1 RNA
OT  - antiviral immunity
OT  - dendritic cells
OT  - pattern recognition receptor
OT  - type I IFN
OT  - viral sensing
EDAT- 2020/02/11 06:00
MHDA- 2021/02/20 06:00
PMCR- 2020/01/01
CRDT- 2020/02/11 06:00
PHST- 2019/08/02 00:00 [received]
PHST- 2020/01/06 00:00 [accepted]
PHST- 2020/02/11 06:00 [entrez]
PHST- 2020/02/11 06:00 [pubmed]
PHST- 2021/02/20 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.00008 [doi]
PST - epublish
SO  - Front Immunol. 2020 Jan 23;11:8. doi: 10.3389/fimmu.2020.00008. eCollection 2020.