2014
DOI: 10.1371/journal.pone.0106188
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Identification of Toll-Like Receptor 9 as Parapoxvirus Ovis-Sensing Receptor in Plasmacytoid Dendritic Cells

Abstract: Parapoxvirus ovis (PPVO) is known for its immunostimulatory capacities and has been successfully used to generate vector vaccines effective especially in non-permissive host species. Murine conventional and plasmacytoid dendritic cells (cDC and pDC) are able to recognize PPVO. The PPVO-sensing receptor on pDC is hitherto unknown. In this study we aimed to define the pattern recognition receptor responsible for the activation of murine pDC by inactivated and replication-competent PPVO. We show that PPVO-induced… Show more

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Cited by 17 publications
(18 citation statements)
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References 43 publications
(71 reference statements)
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“…induction of IFN-α, INF-γ, and TNF-α release, activation of immune cells including dendritic cells, NK cells, CD4+, and CD8+ T-cells (reviewed in [ 13 ]). Albeit TLR-9 has been described as being the “sensing” receptor for iPPVO [ 28 ] the virus mediates the stimulation of the immune system by addressing TLR-dependent and -independent pathways [ 29 ]. The activation of the immune system by iPPVO in general and AIC649 in particular translates into antiviral efficacy in the HBV tg mouse model [ 15 , 17 ].…”
Section: Discussionmentioning
confidence: 99%
“…induction of IFN-α, INF-γ, and TNF-α release, activation of immune cells including dendritic cells, NK cells, CD4+, and CD8+ T-cells (reviewed in [ 13 ]). Albeit TLR-9 has been described as being the “sensing” receptor for iPPVO [ 28 ] the virus mediates the stimulation of the immune system by addressing TLR-dependent and -independent pathways [ 29 ]. The activation of the immune system by iPPVO in general and AIC649 in particular translates into antiviral efficacy in the HBV tg mouse model [ 15 , 17 ].…”
Section: Discussionmentioning
confidence: 99%
“…AIC649, an inactivated parapoxvirus ovis particle preparation, targets antigen presenting cells via TLR9 and leads to cytokine release, including IFN-α [93,94]. The antiviral efficacy of AIC649 was evaluated in woodchucks during 36 weeks of intravenous/intramuscular administration, alone or in combination with ETV during the initial 12 weeks [95].…”
Section: Tlr Agonistsmentioning
confidence: 99%
“…Another TLR9 stimulator is AIC649, an inactivated parapoxvirus ovis (PPVO) particle preparation under development by AiCuris (Anti-infective Cures GmbH, Wuppertal, Germany) for the treatment of human CHB. Since PPVO has a CG-rich double-stranded DNA genome, TLR9 in murine pDCs is the main receptor sensing AIC649 following complement opsonization and cellular uptake of viral particles [ 54 , 55 ] (reviewed in [ 56 ]). Stimulation of TLR9 but not of TLR2 and TLR4 then elicits and releases type I IFNs via the myeloid differentiation primary response gene 88 (MyD88) pathway [ 54 , 55 ].…”
Section: Introductionmentioning
confidence: 99%