PMID- 19543380
OWN - NLM
STAT- MEDLINE
DCOM- 20090916
LR  - 20231213
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 5
IP  - 6
DP  - 2009 Jun
TI  - Innate immune sensing of modified vaccinia virus Ankara (MVA) is mediated by 
      TLR2-TLR6, MDA-5 and the NALP3 inflammasome.
PG  - e1000480
LID - 10.1371/journal.ppat.1000480 [doi]
LID - e1000480
AB  - Modified vaccinia virus Ankara (MVA) is an attenuated double-stranded DNA 
      poxvirus currently developed as a vaccine vector against HIV/AIDS. Profiling of 
      the innate immune responses induced by MVA is essential for the design of vaccine 
      vectors and for anticipating potential adverse interactions between naturally 
      acquired and vaccine-induced immune responses. Here we report on innate immune 
      sensing of MVA and cytokine responses in human THP-1 cells, primary human 
      macrophages and mouse bone marrow-derived macrophages (BMDMs). The innate immune 
      responses elicited by MVA in human macrophages were characterized by a robust 
      chemokine production and a fairly weak pro-inflammatory cytokine response. 
      Analyses of the cytokine production profile of macrophages isolated from knockout 
      mice deficient in Toll-like receptors (TLRs) or in the adapter molecules MyD88 
      and TRIF revealed a critical role for TLR2, TLR6 and MyD88 in the production of 
      IFNbeta-independent chemokines. MVA induced a marked up-regulation of the 
      expression of RIG-I like receptors (RLR) and the IPS-1 adapter (also known as 
      Cardif, MAVS or VISA). Reduced expression of RIG-I, MDA-5 and IPS-1 by shRNAs 
      indicated that sensing of MVA by RLR and production of IFNbeta and 
      IFNbeta-dependent chemokines was controlled by the MDA-5 and IPS-1 pathway in the 
      macrophage. Crosstalk between TLR2-MyD88 and the NALP3 inflammasome was essential 
      for expression and processing of IL-1beta. Transcription of the Il1b gene was 
      markedly impaired in TLR2(-/-) and MyD88(-/-) BMDM, whereas mature and secreted 
      IL-1beta was massively reduced in NALP3(-/-) BMDMs or in human THP-1 macrophages 
      with reduced expression of NALP3, ASC or caspase-1 by shRNAs. Innate immune 
      sensing of MVA and production of chemokines, IFNbeta and IL-1beta by macrophages 
      is mediated by the TLR2-TLR6-MyD88, MDA-5-IPS-1 and NALP3 inflammasome pathways. 
      Delineation of the host response induced by MVA is critical for improving our 
      understanding of poxvirus antiviral escape mechanisms and for designing new MVA 
      vaccine vectors with improved immunogenicity.
FAU - Delaloye, Julie
AU  - Delaloye J
AD  - Department of Medicine, Infectious Diseases Service, Centre Hospitalier 
      Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
FAU - Roger, Thierry
AU  - Roger T
FAU - Steiner-Tardivel, Quynh-Giao
AU  - Steiner-Tardivel QG
FAU - Le Roy, Didier
AU  - Le Roy D
FAU - Knaup Reymond, Marlies
AU  - Knaup Reymond M
FAU - Akira, Shizuo
AU  - Akira S
FAU - Petrilli, Virginie
AU  - Petrilli V
FAU - Gomez, Carmen E
AU  - Gomez CE
FAU - Perdiguero, Beatriz
AU  - Perdiguero B
FAU - Tschopp, Jurg
AU  - Tschopp J
FAU - Pantaleo, Giuseppe
AU  - Pantaleo G
FAU - Esteban, Mariano
AU  - Esteban M
FAU - Calandra, Thierry
AU  - Calandra T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20090619
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Toll-Like Receptors)
RN  - EC 3.6.1.- (RIGI protein, human)
RN  - EC 3.6.1.- (Ddx58 protein, mouse)
RN  - EC 3.6.1.- (IFIH1 protein, human)
RN  - EC 3.6.1.- (Ifih1 protein, mouse)
RN  - EC 3.6.4.13 (DEAD Box Protein 58)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
RN  - EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1)
SB  - IM
RIN - PLoS Pathog. 2022 Jan 25;18(1):e1010263. PMID: 35077525
MH  - Animals
MH  - Carrier Proteins/genetics/*immunology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chick Embryo
MH  - Cytokines/biosynthesis/immunology
MH  - DEAD Box Protein 58
MH  - DEAD-box RNA Helicases/genetics/*immunology
MH  - Endocytosis
MH  - Female
MH  - Genetic Vectors/genetics/immunology
MH  - HeLa Cells
MH  - Humans
MH  - Immunity, Innate/*physiology
MH  - Interferon-Induced Helicase, IFIH1
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/genetics/*immunology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Receptors, Immunologic
MH  - Signal Transduction
MH  - Toll-Like Receptors/genetics/*immunology
MH  - Vaccinia virus/genetics/*immunology
PMC - PMC2691956
COIS- The authors have declared that no competing interests exist.
EDAT- 2009/06/23 09:00
MHDA- 2009/09/17 06:00
PMCR- 2009/06/19
CRDT- 2009/06/23 09:00
PHST- 2008/11/12 00:00 [received]
PHST- 2009/05/21 00:00 [accepted]
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2009/09/17 06:00 [medline]
PHST- 2009/06/19 00:00 [pmc-release]
AID - 08-PLPA-RA-1419R3 [pii]
AID - 10.1371/journal.ppat.1000480 [doi]
PST - ppublish
SO  - PLoS Pathog. 2009 Jun;5(6):e1000480. doi: 10.1371/journal.ppat.1000480. Epub 2009 
      Jun 19.