Organization, structure and expression of murine interferon alpha genes

Zwarthoff, Ellen C.; Mooren, A. T. A.; Trapman, Jan

doi:10.1093/nar/13.3.791

Cited by 95 publications

(50 citation statements)

References 42 publications

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“…All 13 human IFN-a subtype genes are located on chromosome 9, whereas the murine genome encodes for 14 subtypes on chromosome 4. All type I IFN have similarities in structure, like the lack of introns or the length of the protein (161-167 amino acids), and their protein sequence is highly conserved (75-99% amino acid sequence identity) (Zwarthoff et al, 1985;Hardy et al, 2004). Interestingly, they all bind the same ubiquitously expressed receptor, called IFNAR, but they still differ in their biological activities.…”

Section: Ifn-a Subtypesmentioning

confidence: 99%

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Gibbert

Schlaak

Yang

et al. 2013

British J Pharmacology

154

138

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During most viral infections, the immediate host response is characterized by an induction of type I IFN. These cytokines have various biological activities, including anti‐viral, anti‐proliferative and immunomodulatory effects. After induction, they bind to their IFN‐α/β receptor, which leads to downstream signalling resulting in the expression of numerous different IFN‐stimulated genes. These genes encode anti‐viral proteins that directly inhibit viral replication as well as modulate immune function. Thus, the induction of type I IFN is a very powerful tool for the host to fight virus infections. Many viruses evade this response by various strategies like the direct suppression of IFN induction or inhibition of the IFN signalling pathway. Therefore, the therapeutic application of exogenous type I IFN or molecules that induce strong IFN responses should be of great potential for future immunotherapies against viral infections. Type I IFN is currently used as a treatment in chronic hepatitis B and C virus infection, but as yet is not widely utilized for other viral infections. One reason for this restricted clinical use is that type I IFN belongs to a multigene family that includes 13 different IFN‐α subtypes and IFN‐β, whose individual anti‐viral and immunomodulatory properties have so far not been investigated in detail to improve IFN therapy against viral infections in humans. In this review, we summarize the recent achievements in defining the distinct biological functions of type I IFN subtypes in cell culture and in animal models of viral infection as well as their clinical usage in chronic hepatitis virus infections.

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Section: Ifn-a Subtypesmentioning

confidence: 99%

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Gibbert

Schlaak

Yang

et al. 2013

British J Pharmacology

154

138

View full text Add to dashboard Cite

show abstract

“…It appeared that all the natural and hybrid IFN genes coded for IFN subspecies with biological activity on mouse as well as on hamster cells. Surprisingly, the ~4 gene, which contains an in-phase deletion of 15 nucleotides (Zwarthoff et al, 1985b), also encoded a biologically active IFN. Moreover, ~4 and the c~2~4 hybrid produced considerably more antiviral activity on mouse cells than the other genes.…”

Section: Expression In Cos Cellsmentioning

confidence: 99%

Properties of Natural and Hybrid Murine Alpha Interferons

Heuvel

Bosveld

Mooren

et al. 1986

Journal of General Virology

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SUMMARYFour natural murine interferon-~ genes (MuIFN-cd, -~2, -~4 and -cc6) and four hybrid genes (crick4, ~2cM, ~4cd and cc4~2) were transiently expressed in monkey COS cells under the transcriptional control of the simian virus 40 early promoter. The proteins were labelled with [35S]methionine during a 16 h incubation and proteins secreted by the cells during this period were separated by polyacrylamide gel electrophoresis and subsequently visualized by fluorography. Under the conditions used, the IFNs represented 5 to 10~ of the total amount of secreted proteins. All genes were found to encode biologically active IFN subspecies, including ~4 which has a deletion of five amino acids. When the specific activities of the proteins were compared, it appeared that the specific antiviral activity of c~4 on mouse cells was three-to sixfold higher than the activities of the other natural IFN subspecies. The specific activities of the hybrid proteins were similar to those of the natural proteins, except for the ~2c~4 hybrid which had a higher specific activity than the original proteins. The ability of the natural and hybrid subspecies to protect hamster cells against viral infection was determined using MuIFN-~I as a standard. Large differences in activity were found, with ~6 as the most and ~4 as the least active subspecies.

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“…Murine IFN−αs have over 70% sequence identity with human IFN−αs [9,10]. However, there is only one IFN−β subtype expressed in both humans and mice [11]. Human IFN−β has 63% homology with mouse IFN−β but only 30% homology with the IFN−αs and so they are closer to each other than to the IFN−αs in their own species.…”

Section: Ifn Typesmentioning

confidence: 99%

Interferons as Biomarkers and Effectors: Lessons Learned from Animal Models

2012

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Interferons (IFNs) comprise type I, II and III families with multiple subtypes. Via transcription of IFNstimulated genes (ISGs), IFNs can exert multiple biological effects on the cell. In infectious and chronic inflammatory diseases, the IFNs and their ISG sets can be potentially utilized as biomarkers of disease outcome. Animal models allow investigations into disease pathogenesis and gene knockout models have proved cause and effect relationships of molecules related to the IFN response. Sets of IFN subtypes and their ISG products provide immunological signature patterns for different viral and other diseases. In this article, we give an overview of IFNs in several virus infection models and autoimmune diseases of medical relevance. Lessons learned from animal models inform us of IFN system parameters as indicators of disease outcome and whether clinical research is warranted. Moreover, validated IFN biomarkers for prognosis enhance our understanding of therapeutic and vaccine development.

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Organization, structure and expression of murine interferon alpha genes

Cited by 95 publications

References 42 publications

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Properties of Natural and Hybrid Murine Alpha Interferons

Interferons as Biomarkers and Effectors: Lessons Learned from Animal Models

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