Hepatitis A Virus Suppresses RIG-I-Mediated IRF-3 Activation To Block Induction of Beta Interferon

Fensterl, Volker; Grotheer, D.; Berk, Iris; Schlemminger, Stefanie; Vallbracht, Angelika; Dotzauer, Andreas

doi:10.1128/jvi.79.17.10968-10977.2005

Cited by 87 publications

(77 citation statements)

References 55 publications

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“…However, HAV never establishes long-term persistent infection and is always eliminated by host defenses. Nonetheless, recent reports indicate that HAV also is capable of blocking RIG-I mediated IRF3 activation and IFN-␤ expression (16,17). We show here that HAV infection strongly downregulates the expression of MAVS, ablating signaling through the MDA5 pathway.…”

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confidence: 47%

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Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor

Yang

Liang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

291

279

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confidence: 47%

“…Recent reports suggest that HAV infection blocks induction of IFN-␤ synthesis through the RIG-I pathway by preventing virus activation of IRF3 (16,17). To confirm this, we studied fetal rhesus kidney (FRhK-4) cells infected with a cell culture-adapted variant of HAV, HM175/18f (18).…”

Section: Virus Activation Of Irf3 Is Blocked By Autonomous Replicatiomentioning

confidence: 99%

Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor

Yang

Liang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

291

279

View full text Add to dashboard Cite

show abstract

“…Although the mitochondrial localization of MAVS may allow the host immune system to detect many viruses that replicate in intracellular membrane locations proximal to the mitochondria, it also may render MAVS vulnerable to viral attack. For example, it has recently been shown that the hepatitis A virus (HAV) inhibits IFN response at a step downstream of RIG-I but upstream of TBK1͞IKK (28), raising the possibility that MAVS may be a target of a HAV protein. Future studies should uncover more examples of host-pathogen interaction that revolve around the battle for MAVS to gain control of the host immune system.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity

Sun

Seth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

752

638

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“…Several lines of evidence indicate that intracellular viral infection is detected by RIG-I and that this protein initiates events that activate host-associated antiviral responses (9,(32)(33)(34)(35)). The precise mechanism by which RIG-I activates the innate immune system has been the subject of intense research (10,14,36,37).…”

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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Hepatitis A Virus Suppresses RIG-I-Mediated IRF-3 Activation To Block Induction of Beta Interferon

Cited by 87 publications

References 55 publications

Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor

Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor

Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity

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

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