2014
DOI: 10.3389/fmicb.2014.00504
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Human herpesviruses-encoded dUTPases: a family of proteins that modulate dendritic cell function and innate immunity

Abstract: We have previously shown that Epstein-Barr virus (EBV)-encoded dUTPase can modulate innate immune responses through the activation of TLR2 and NF-κB signaling. However, whether this novel immune function of the dUTPase is specific for EBV or a common property of the Herpesviridae family is not known. In this study, we demonstrate that the purified viral dUTPases encoded by herpes simplex virus type 2 (HSV-2), human herpesvirus-6A (HHV-6A), human herpesvirus-8 (HHV-8) and varicella-zoster virus (VZV) differenti… Show more

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Cited by 35 publications
(66 citation statements)
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References 90 publications
(180 reference statements)
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“…Furthermore, it has been shown that IL-17 serum levels were significantly increased in patients with SLE and positively correlated with SLE Disease Activity Index (SLEDAI) scores [118]. In line with these findings, extensive studies by our group have demonstrated that the EBV dUTPase activates TLR2 in human immune cells [7,27,29] and induces the production of pro-inflammatory T H 1/T H 17 cytokines [7,27,29,30], which have been implicated in the pathogenesis of SLE [113,114]. …”
Section: Herpesviruses Dutpases and Human Diseasementioning
confidence: 72%
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“…Furthermore, it has been shown that IL-17 serum levels were significantly increased in patients with SLE and positively correlated with SLE Disease Activity Index (SLEDAI) scores [118]. In line with these findings, extensive studies by our group have demonstrated that the EBV dUTPase activates TLR2 in human immune cells [7,27,29] and induces the production of pro-inflammatory T H 1/T H 17 cytokines [7,27,29,30], which have been implicated in the pathogenesis of SLE [113,114]. …”
Section: Herpesviruses Dutpases and Human Diseasementioning
confidence: 72%
“…We have demonstrated that the EBV-dUTPase triggers NF-κB activation through engagement of TLR2 homodimers, while the dUTPases expressed by HSV-2, HHV-6A, HHV-8, and VZV require ligation of the TLR2/1 heterodimer complex to activate NF-κB [7,27]. We have also demonstrated that these viral dUTPases are capable of differentially inducing the secretion of the pro-inflammatory T H 1/T H 17 cytokines IL-1β, IL-6, IL-8, IL-12p70, TNF-α, and IFN-γ as well as the anti-inflammatory cytokine IL-10 ( p < 0.001) in human primary immune cells [7,25,26,27].…”
Section: Herpesviruses’ Dutpases and Innate Immunitymentioning
confidence: 99%
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