Lethality of interferon preparations for newborn mice

Gresser, Ion; Tovey, Michaël G.; Maury, Chantal; Chouroulinkov, I

doi:10.1038/258076a0

Cited by 117 publications

(53 citation statements)

References 8 publications

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“…An alternative explanation may be that chIFN-impairs the establishment of the normal gut flora and thereby interferes with nutrient absorption after hatching. It is of interest to note that daily injection of highly concentrated interferon preparations was lethal for newborn mice, with mortality occurring after seven to 14 days of treatment (29).…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Lambda Interferon in Chickens

Reuter

Soubies

Härtle

et al. 2014

J Virol

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Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Lambda Interferon in Chickens

Reuter

Soubies

Härtle

et al. 2014

J Virol

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“…Excessive IFN production is harmful to the host and may cause cell apoptosis or autoimmunity (42)(43)(44)(45)(46). Negative regulators of IFN pathway are known to be important in preventing host cell from producing unwanted IFNs.…”

Section: Discussionmentioning

confidence: 99%

Human Bocavirus VP2 Upregulates IFN-β Pathway by Inhibiting Ring Finger Protein 125–Mediated Ubiquitination of Retinoic Acid–Inducible Gene-I

Luo

Zhang

Zheng

et al. 2013

The Journal of Immunology

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Precise regulation of innate immunity is crucial for maintaining optimal immune responses against infections. Whereas positive regulation of IFN signaling elicits rapid type I IFNs, negative regulation is equally important in preventing the production of superfluous IFNs that can be hazardous to the host. The positive regulators of IFN pathway are known to be the main targets of viruses to antagonize the innate immune system. Whether viruses target the negative regulators of IFN pathway remains to be fully investigated. In this study, we report that the structural protein VP2 of human Bocavirus modulates IFN pathway by targeting the ring finger protein 125 (RNF125), a negative regulator of type I IFN signaling, which conjugates Lys48-linked ubiquitination to retinoic acid–inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. VP2 not only upregulated Sendai virus (SeV)–induced IFNB promoter activity, but also enhanced SeV-induced IFN-β production at both mRNA and protein levels. In agreement, the level of Ser396-phosphorylated IFN regulatory factor 3 stimulated by SeV was enhanced in the presence of VP2. Furthermore, VP2 was demonstrated to physically interact with RNF125, resulting in the reduction of RNF125-mediated ubiquitination and proteasome-dependent degradation of RIG-I. Additional study indicated that endogenous RIG-I degradation was decreased in VP2-expressing cells. Our study delineates a unique phenomenon for aberrant activation of IFN regulatory factor 3 pathway and may represent a new mechanism underlying viral manipulation of the host immune system.

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“…Like most cellular stress responses, innate antiviral immunity must be tightly controlled to prevent unwanted toxicity due to hyperactive signaling (15). Accumulation of IFNs and their downstream effectors can have strong cytotoxic effects (4,5), in many cases requiring their expression to be rapid and transient.…”

Section: Discussionmentioning

confidence: 99%