The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism

Fortier, Marie-Ève; Kent, Stephen; Ashdown, Helen; Poole, Stephen; Boksa, Patricia; Luheshi, Giamal N.

doi:10.1152/ajpregu.00293.2004

Cited by 279 publications

(234 citation statements)

References 49 publications

(51 reference statements)

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“…POLY I:C is thought to mediate inflammation by stimulating IL-1β production (Fortier et al, 2004). In our study, we observed a similar pattern of pro-inflammatory cytokine release within the brain.…”

Section: Discussionsupporting

confidence: 82%

Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats

Galic

Riazi

Henderson

et al. 2009

Neurobiology of Disease

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Viral infections of the CNS and their accompanying inflammation can cause long-term neurological effects, including increased risk for seizures. To examine the effects of CNS inflammation, we infused polyinosinic: polycytidylic acid, intracerebroventricularly to mimic a viral CNS infection in 14 day-old rats. This caused fever and an increase in the pro-inflammatory cytokine, interleukin (IL)-1β in the brain. As young adults, these animals were more susceptible to lithium-pilocarpine and pentylenetetrazol-induced seizures and showed memory deficits in fear conditioning. Whereas there was no alteration in adult hippocampal cytokine levels, we found a marked increase in NMDA (NR2A and C) and AMPA (GluR1) glutamate receptor subunit mRNA expression. The increase in seizure susceptibility, glutamate receptor subunits, and hippocampal IL-1β levels were suppressed by neonatal systemic minocycline. Thus, a novel model of viral CNS inflammation reveals pathophysiological relationships between brain cytokines, glutamate receptors, behaviour and seizures, which can be attenuated by anti-inflammatory agents like minocycline.

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Section: Discussionsupporting

confidence: 82%

Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats

Galic

Riazi

Henderson

et al. 2009

Neurobiology of Disease

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“…2C and D and data not shown). Similarly, we treated monolayers with poly(I·C), a synthetic analogue of double-stranded RNA (35), to evaluate whether the recognition of viral RNA could be responsible for the effect. However, it did not recapitulate platelet adhesion (Fig.…”

Section: Resultsmentioning

confidence: 99%

Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury

Sugiyama

Gamage

Zyla

et al. 2016

J Virol

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Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin ␣ 5 ␤ 1 , implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza. Here, we show that this infection causes platelets to adhere to the lung endothelium. Importantly, blocking platelets using two distinct antiplatelet drugs improved survival in a mouse model of severe influenza infection. Thus, platelet inhibition may constitute a novel therapeutic strategy to improve the host response to severe infections with influenza.

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“…mESCs Can Sense and Respond to dsRNA via Cytosolic Receptors but Fail to Produce Functional IFN␤ and IL6-We further analyzed the responses of mESCs to polyIC, a synthetic analog of viral dsRNA that is widely used to mimic viral infection (32). When directly added to the cell culture, polyIC is expected to bind to TLR3 at the cell surface or to be internalized into the endosomes where it activates TLR3 (33,34).…”

Section: Resultsmentioning

confidence: 99%

“…In some cell types, polyIC can induce IFN␣/␤ via activation of TLR3 at the cell surface or in the endosomes (11,38,39) other responses that are similar to those evoked by viral infection via cytoplasmic dsRNA receptors (32,40). mESCs were unresponsive to polyIC that was directly added to the medium, likely due to the very low level expression of TLR3.…”

Section: Discussionmentioning

confidence: 99%

Mouse Embryonic Stem Cells Are Deficient in Type I Interferon Expression in Response to Viral Infections and Double-stranded RNA

Wang

Wang²,

Paul³

et al. 2013

Journal of Biological Chemistry

118

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Background:The antiviral mechanisms are not known in mESCs. Results: mESCs are susceptible to viral infections and dsRNA-inhibited cell proliferation but do not express type I interferons. Conclusion: mESCs have underdeveloped mechanisms for type I interferon expression. Significance: The findings are important for understanding the development of antiviral mechanisms in ESCs and stem cell physiology.

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The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism

Abstract: . The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism.

Cited by 279 publications

References 49 publications

Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats

Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats

Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury

Mouse Embryonic Stem Cells Are Deficient in Type I Interferon Expression in Response to Viral Infections and Double-stranded RNA

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