Antiviral innate immunity pathways

Seth, Rashu B.; Sun, Lijun; Chen, Zhijian J.

doi:10.1038/sj.cr.7310019

Cited by 425 publications

(387 citation statements)

References 35 publications

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“…Additionally, mitochondria are key players in apoptosis (1,15,57), innate immune defense (51), generation of reactive nitrogenand oxygen species (RNS/ROS; Refs. 2,18,47,58), transduction of electrical signals (23,54), and calcium homeostasis (7,48,67).…”

mentioning

confidence: 99%

Human NADH:ubiquinone oxidoreductase deficiency: radical changes in mitochondrial morphology?

Koopman¹,

Verkaart²,

Visch³

et al. 2007

American Journal of Physiology-Cell Physiology

122

116

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function of NADH:ubiquinone oxidoreductase or complex I (CI), the first and largest complex of the mitochondrial oxidative phosphorylation system, has been implicated in a wide variety of human disorders. To demonstrate a quantitative relationship between CI amount and activity and mitochondrial shape and cellular reactive oxygen species (ROS) levels, we recently combined native electrophoresis and confocal and video microscopy of dermal fibroblasts of healthy control subjects and children with isolated CI deficiency. Individual mitochondria appeared fragmented and/or less branched in patient fibroblasts with a severely reduced CI amount and activity (class I), whereas patient cells in which these latter parameters were only moderately reduced displayed a normal mitochondrial morphology (class II). Moreover, cellular ROS levels were significantly more increased in class I compared with class II cells. We propose a mechanism in which a mutation-induced decrease in the cellular amount and activity of CI leads to enhanced ROS levels, which, in turn, induce mitochondrial fragmentation when not appropriately counterbalanced by the cell's antioxidant defense systems. complex I; reactive oxygen species; microscopy; fluorescence MITOCHONDRIAL FUNCTION AND COMPLEX I DEFICIENCY

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mentioning

confidence: 99%

Human NADH:ubiquinone oxidoreductase deficiency: radical changes in mitochondrial morphology?

Koopman¹,

Verkaart²,

Visch³

et al. 2007

American Journal of Physiology-Cell Physiology

122

116

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“…The precise mechanism by which RIG-I activates the innate immune system has been the subject of intense research (10,14,36,37). The events that follow the binding of dsRNA by RIG-I include the homodimerization of IFN regulatory factor 3 and the subsequent up-regulation and expression of IFN genes (9).…”

Section: Discussionmentioning

confidence: 99%

IFN-ε Mediates TNF-α-Induced STAT1 Phosphorylation and Induction of Retinoic Acid-Inducible Gene-I in Human Cervical Cancer Cells

Matsumiya

Prescott

Stafforini

2007

The Journal of Immunology

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Retinoic acid inducible gene-I (RIG-I) plays important roles during innate immune responses to viral infections and as a transducer of cytokine signaling. The mechanisms of RIG-I up-regulation after cytokine stimulation are incompletely characterized. It was previously reported that IFN–γ induces the expression of RIG-I in endothelial cells. In this study, we characterized the mechanism of type I IFN-mediated up-regulation of RIG-I in HeLa cells and found that, in addition to type I IFN, TNF-α, a cytokine that regulates innate immune responses, induced expression of RIG-I. To investigate whether TNF-α- and type I IFN-mediated up-regulations of RIG-I were causally related, we studied the kinetics of these responses. Our results were consistent with a model in which TNF-α functioned upstream of type I IFNs. The ability of TNF-α to up-regulate RIG-I required protein synthesis, expression of functional type I IFNRs, and STAT1 signaling. We also found that IFN-ε was the only IFN isoform expressed constitutively in HeLa cells and that its expression was up-regulated in response to stimulation with TNF-α. The mechanism of up-regulation involved stabilization of IFN-ε mRNA in the absence of transcriptional activation. Silencing the expression of IFN-ε attenuated STAT1 expression and phosphorylation and inhibited RIG-I expression, providing additional support for the participation of IFN-ε upstream of STAT1. Our findings support a sequential mechanism whereby TNF-α leads to stabilization of IFN-ε mRNA, increased IFN-ε synthesis, engagement of type I IFNRs, increased STAT1 expression and phosphorylation, and up-regulation of RIG-I expression. These findings have implications for our understanding of the immune responses that follow cytokine stimulation.

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“…These kinases liberate transcription factors such as nuclear factor κB (NF-κB) and IFN regulatory factor 3/7, leading to the induction of type I IFNs and pro-inflammatory cytokines [10,11]. Once secreted, type I IFNs rapidly induce multiple IFN-stimulated genes [12,13] that orchestrate an antiviral state in the cells [14]. Due to its prominent role in propagating antiviral signaling [15,16], MAVS is subject to meticulous modulations by different proteins [17], which fine-tune the cellular responses over the course of viral infection [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Poly(C)-binding protein 1 (PCBP1) mediates housekeeping degradation of mitochondrial antiviral signaling (MAVS)

et al. 2011

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Mitochondrial antiviral signaling (MAVS) is a key adaptor in cellular antiviral innate immunity. We previously identified poly(C)-binding protein 2 (PCBP2) as a feedback inhibitor of MAVS that facilitates its degradation after viral infection, but little is known about the regulatory potential of poly(C)-binding protein 1 (PCBP1), which highly resembles PCBP2. Here we report that PCBP1 mediates housekeeping degradation of MAVS using the same mechanism as PCBP2 employs. Overexpression of PCBP1 impairs MAVS-mediated antiviral responses, while knockdown of PCBP1 exerts the opposite effect. The suppression is due to PCBP1-induced MAVS degradation. We observe that PCBP1 and PCBP2 show synergy in MAVS inhibition, but their expression patterns are distinct: PCBP1 is stably and abundantly expressed, while PCBP2 shows low basal expression with rapid induction after infection. Individual knockdown and subcellular fractionation analyses reveal that unlike the postinfection inhibitor PCBP2, PCBP1 continuously eliminates cellular MAVS. Our findings unravel a critical role of PCBP1 in regulating MAVS for both finetuning the antiviral immunity and preventing inflammation.

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Antiviral innate immunity pathways

Cited by 425 publications

References 35 publications

Human NADH:ubiquinone oxidoreductase deficiency: radical changes in mitochondrial morphology?

Human NADH:ubiquinone oxidoreductase deficiency: radical changes in mitochondrial morphology?

IFN-ε Mediates TNF-α-Induced STAT1 Phosphorylation and Induction of Retinoic Acid-Inducible Gene-I in Human Cervical Cancer Cells

Poly(C)-binding protein 1 (PCBP1) mediates housekeeping degradation of mitochondrial antiviral signaling (MAVS)

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