Characterization of Interferon-α 13, a Novel Constitutive Murine Interferon-α Subtype

Pesch, Vincent Van; Michiels, Thomas

doi:10.1074/jbc.m302554200

Cited by 40 publications

(45 citation statements)

References 57 publications

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“…B16 melanoma cells, kindly provided by Luc Pilotte and Benoît Van den Eynde (Ludwig Institute for Cancer Research, Brussels, Belgium) were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum, 100 IU of penicillin per ml, and 100 g of streptomycin (Invitrogen, Life-technologies) per ml and supplemented with 116 g of L-arginine per ml, 36 g of L-asparagine per ml, and 216 g of L-glutamine per ml. BHK-21, COS-7, BALB/ 3T3, and L929 cells were cultured as described previously (44).…”

Section: Methodsmentioning

confidence: 99%

“…For example, murine IFN-␣4 has been shown to be expressed early after viral infection, without a requirement for IRF-7 synthesis and activation, whereas the expression of other IFN-␣ subtypes depends on an autocrine or paracrine feedback loop mediated by this factor (27,36). We recently showed that IFN-␣13 was constitutively expressed at background levels in mouse cells (44). This IFN differs from other IFN-␣ subtypes by the fact that its expression is not influenced by viral infection.…”

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confidence: 99%

“…They are coded by an intronless multigene family clustered on murine chromosome 4 and in human chromosome 9. One IFN-␤ and multiple IFN-␣ genes were found in the mouse and human genomes (11,13,14,15,22,25,30,35,37,39,41,44,47,50). Other IFN-␣/␤ genes described include the murine limitin gene and the human IFN-gene, as well as the IFN-and IFN-ε/ genes that were found in both the human and murine genomes (Table 1) (2,9,24,32,46).…”

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confidence: 99%

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Characterization of the Murine Alpha Interferon Gene Family

Pesch

Lanaya

Renauld

et al. 2004

J Virol

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177

156

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Mouse and human genomes carry more than a dozen genes coding for closely related alpha interferon (IFN-␣) subtypes. IFN-␣, as well as IFN-␤, IFN-, IFN-, and limitin, are thought to bind the same receptor, raising the question of whether different IFN subtypes possess specific functions. As some confusion existed in the identity and characteristics of mouse IFN-␣ subtypes, the availability of data from the mouse genome sequence prompted us to characterize the murine IFN-␣ family. A total of 14 IFN-␣ genes were detected in the mouse genome, in addition to three IFN-␣ pseudogenes. Four IFN-␣ genes (IFN-␣1, IFN-␣7/10, IFN-␣8/6, and IFN-␣11) exhibited surprising allelic divergence between 129/Sv and C57BL/6 mice. All IFN-␣ subtypes were found to be stable at pH 2 and to exhibit antiviral activity. Interestingly, some IFN subtypes (IFN-␣4, IFN-␣11, IFN-␣12, IFN-␤, and limitin) showed higher biological activity levels than others, whereas IFN-␣7/10 exhibited lower activity. Most murine IFN-␣ turned out to be N-glycosylated. However, no correlation was found between N-glycosylation and activity. The various IFN-␣ subtypes displayed a good correlation between their antiviral and antiproliferative potencies, suggesting that IFN-␣ subtypes did not diverge primarily to acquire specific biological activities but probably evolved to acquire specific expression patterns. In L929 cells, IFN genes activated in response to poly(I•C) transfection or to viral infection were, however, similar.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Characterization of the Murine Alpha Interferon Gene Family

Pesch

Lanaya

Renauld

et al. 2004

J Virol

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177

156

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“…Analysis of transgenic mice overexpressing IFN-␣ in the CNS revealed that CA1 and CA2 but not CA3 neurons of the hippocampus responded by expressing the IFN-inducible Mx1 gene (13). Recently, Cho et al reported an important difference in responsiveness between granule cell neurons of the cerebellum previously (23). IFN-was quantified by the same method using LKR-10 cells, which readily respond to IFN-.…”

Section: The Type I Interferon (Ifn) Response Is An Innate Immune Defmentioning

confidence: 99%

Inefficient Type I Interferon-Mediated Antiviral Protection of Primary Mouse Neurons Is Associated with the Lack of Apolipoprotein L9 Expression

Kreit

Stolzmann

Knoops

et al. 2014

J Virol

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We examined the antiviral response promoted by type I interferons (IFN) in primary mouse neurons. IFN treatment of neuron cultures strongly upregulated the transcription of IFN-stimulated genes but conferred a surprisingly low resistance to infection by neurotropic viruses such as Theiler's murine encephalomyelitis virus (TMEV) or vesicular stomatitis virus (VSV). Response of primary mouse neurons to IFN treatment was heterogeneous, as many neurons failed to express the typical IFN response marker Mx1 after IFN treatment. This heterogeneous response of primary neurons correlated with a low level of basal expression of IFN-stimulated genes, such as Stat1, that are involved in signal transduction of the IFN response. In addition, transcriptomic analysis identified 15 IFN-responsive genes whose expression was low in IFN-treated primary neurons compared to that of primary fibroblasts derived from the same mice (Dhx58, Gvin1, Sp100, Ifi203 isoforms 1 and 2, Irgm2, Lgals3bp, Ifi205, Apol9b, Ifi204, Ifi202b, Tor3a, Slfn2, Ifi35, Lgals9). Among these genes, the gene coding for apolipoprotein L9b (Apol9b) displayed antiviral activity against Theiler's virus when overexpressed in L929 cells or in primary neurons. Accordingly, knocking down Apol9b expression in L929 cells increased viral replication. Therefore, we identified a new antiviral protein induced by interferon, ApoL9b, whose lack of expression in primary neurons likely contributes to the high sensitivity of these cells to viral infection. IMPORTANCE The type I interferon (IFN) response is an innate immune defense mechanism that is critical to contain viral infection in the hostuntil an adaptive immune response can be mounted. Neurons are a paradigm for postmitotic, highly differentiated cells. Our data show that primary mouse neurons that are exposed to type I interferon remain surprisingly susceptible to viral infection. On one hand, the low level of basal expression of some factors in neurons might prevent a rapid response of these cells. On the other hand, some genes that are typically activated by type I interferon in other cell types are expressed at much lower levels in neurons. Among these genes is the gene encoding apolipoprotein L9, a protein that proved to have antiviral activity against the neurotropic Theiler's murine encephalomyelitis virus. Our data suggest important functional differences in the IFN response mounted by specific cell populations.

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“…Taken together, these observations indicate that neither STAT4, STAT1, nor STAT3 activation, even together, are sufficient to mediate the ). B, BWLICR2 stable transfectants were stimulated with control medium (1% mock HEK293 SN), IFN-1 (600 units/ml), or IFN␤ (1% HEK293 SN) for 4 h. Total RNA was extracted, and the IRF-7 mRNA was amplified by reverse transcriptase-PCR as described (29).…”

Section: Ifn-1/il-28r Signaling Mechanismsmentioning

confidence: 99%

Role of the Interleukin (IL)-28 Receptor Tyrosine Residues for Antiviral and Antiproliferative Activity of IL-29/Interferon-λ1

Dumoutier

Tounsi

Michiels

et al. 2004

Journal of Biological Chemistry

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279

232

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Interferon (IFN)-1, -2, and -3 are the latest members of the class II cytokine family and were shown to have antiviral activity. Their receptor is composed of two chains, interleukin-28R/likely interleukin or cytokine or receptor 2 (IL-28R/LICR2) and IL-10R␤, and mediates the tyrosine phosphorylation of STAT1, STAT2, STAT3, and STAT5. Here, we show that activation of this receptor by IFN-1 can also inhibit cell proliferation and induce STAT4 phosphorylation, further extending functional similarities with type I IFNs. We used IL-28R/ LICR2-mutated receptors to identify the tyrosines required for STAT activation, as well as antiproliferative and antiviral activities. We found that IFN-1-induced STAT2 tyrosine phosphorylation is mediated through tyrosines 343 and 517 of the receptor, which showed some similarities with tyrosines from type I IFN receptors involved in STAT2 activation. These two tyrosines were also responsible for antiviral and antiproliferative activities of IFN-1. By contrast, STAT4 phosphorylation (and to some extent STAT3 activation) was independent from IL-28R/LICR2 tyrosine residues. Taken together, these observations extend the functional similarities between IFN-s and type I IFNs and shed some new light on the mechanisms of activation of STAT2 and STAT4 by these cytokines.The interleukin-28 receptor (IL-28R, also named LICR2 and CRF2-12) 1 is a member of the class II cytokine receptor family (CRF2) (1-3), which includes receptors for type I and type II IFNs (IFNAR1, IFNAR2, IFNGR1, and IFNGR2), tissue factor, and receptors for IL-10-related cytokines: IL-10R␣, IL-22R/ CRF2-9, IL-10R␤/CRF2-4, IL-20R␣/CRF2-8, IL-20R␤/CRF2-11, and IL-28R/LICR2 (4 -7). When IL-28R associates with IL-10R␤, it creates a high affinity binding complex for IFN-1, -2, and -3 (also called IL-29, IL-28a, and IL-28b) (2, 3). These cytokines share limited sequence similarity with type I IFNs. Like type I IFNs, they are expressed by human peripheral blood mononuclear cells and dendritic cells upon infection with viruses or stimulation with poly(I:C) (2, 3, 8).Although they use distinct receptor chains, which have no detectable homology in their intra-cytoplasmic domain, type I IFNs and IFN-s activate similar signal transduction pathways. Chimeric receptors containing the intracellular portion of IL-28R/LICR2 could mediate JAK1 (Janus kinase 1) activation, as well as tyrosine phosphorylation of STAT factors (1, 2), including STAT2, whose activation was considered to be a specific characteristic of the type I IFN response (9, 10).Most importantly, IFN-1, -2, and -3 protected several cell lines against viral infection and up-regulated major histocompatibility complex class I antigen expression (2, 3). Receptors for type I IFNs are composed of two chains, IFNAR1 and IFNAR2, in which 3 tyrosines seem to be essential to recruit STAT2: Tyr 466 in IFNAR1, and Tyr 337 and Tyr 512 in IFNAR2 (11, 12). Here, we introduced point mutations into the cytoplasmic domain of IL-28R/LICR2 to determine which tyrosines are involved in different ...

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Characterization of Interferon-α 13, a Novel Constitutive Murine Interferon-α Subtype

Cited by 40 publications

References 57 publications

Characterization of the Murine Alpha Interferon Gene Family

Characterization of the Murine Alpha Interferon Gene Family

Inefficient Type I Interferon-Mediated Antiviral Protection of Primary Mouse Neurons Is Associated with the Lack of Apolipoprotein L9 Expression

Role of the Interleukin (IL)-28 Receptor Tyrosine Residues for Antiviral and Antiproliferative Activity of IL-29/Interferon-λ1

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