scholarly journals Novel Characteristics of the Function and Induction of Murine p56 Family Proteins

2008 ◽  
Vol 82 (22) ◽  
pp. 11045-11053 ◽  
Author(s):  
Volker Fensterl ◽  
Christine L. White ◽  
Michifumi Yamashita ◽  
Ganes C. Sen
Keyword(s):  
Dendritic Cells ◽  
Virus Infection ◽  
Mesangial Cells ◽  
Sendai Virus ◽  
Family Members ◽  
Encephalomyocarditis Virus ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Myeloid Dendritic Cells ◽  
Differential Properties

ABSTRACT The interferon-stimulated gene 56 (ISG56) family is induced strongly in response to virus infection, interferons (IFNs) and double-stranded RNA (dsRNA). In the mouse, this family comprises three members, ISG56, ISG54, and ISG49, which are clustered on chromosome 19 and encode the corresponding proteins p56, p54, and p49. Here, we report differential properties of these proteins and their distinct induction patterns in different cell types. All three murine proteins bound to the c-subunit of the translation initiation factor eIF3, but unlike the other members, p49 did not inhibit protein synthesis. Using a newly raised antibody, we demonstrated that both in vitro and in vivo, p49 expression was strongly induced by IFN, dsRNA, and Sendai virus. However, in kidney mesangial cells, as opposed to podocytes, encephalomyocarditis virus, vesicular stomatitis virus, or extracellular dsRNA did not induce any of the p56 family proteins, although they were robustly expressed after Sendai virus infection or dsRNA transfection. Furthermore, protein-specific differences in the regulation of p56 family members became evident in various leukocyte types: all three proteins were induced by IFN in T cells, but in B cells p56 and ISG56 mRNA could not be detected. Similarly, p56 was selectively uninducible in plasmacytoid dendritic cells, whereas in myeloid dendritic cells, all three family members were expressed. These results revealed novel cell type-, inducer-, and gene-specific regulation of the ISG56 family of genes.

scholarly journals Sindbis Virus Translation Is Inhibited by a PKR/RNase L-Independent Effector Induced by Alpha/Beta Interferon Priming of Dendritic Cells

2005 ◽  
Vol 79 (3) ◽  
pp. 1487-1499 ◽  
Author(s):  
K. D. Ryman ◽  
K. C. Meier ◽  
E. M. Nangle ◽  
S. L. Ragsdale ◽  
N. L. Korneeva ◽  
...  
Keyword(s):  
Virus Infection ◽  
Sindbis Virus ◽  
Encephalomyocarditis Virus ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Rnase L ◽  
Α Subunit ◽  
Early Effect ◽  
Beta Interferon ◽  
Alpha Beta

ABSTRACT The tropism of Sindbis virus (SB) for cells of the dendritic cell (DC) lineage and the virulence of SB in vivo are largely determined by the efficacy of alpha/beta interferon (IFN-α/β)-mediated antiviral responses. These responses are essentially intact in the absence of PKR and/or RNase L (K. D. Ryman, L. J. White, R. E. Johnston, and W. B. Klimstra, Viral Immunol. 15:53-76, 2002). In the present studies, we investigated the nature of antiviral effects and identity of antiviral effectors primed by IFN-α/β treatment of bone marrow-derived DCs (BMDCs) generated from mice deficient in PKR and RNase L (TD). IFN-α/β priming exerted significant antiviral activity at very early stages of SB replication and most likely inhibited the initial translation of infecting genomes. The early effect targeted cap-dependent translation as protein synthesis from an SB-like and a simple RNA were inhibited by interferon treatment, but an encephalomyocarditis virus internal ribosome entry site-driven element exhibited no inhibition. Phosphorylation of the α subunit of eukaryotic translation initiation factor 2 was defective after virus infection of TD cells, suggesting other mechanisms of translation inhibition. To identify components of these alternative antiviral pathway(s), we have compared global gene regulation in BMDCs derived from normal 129 Sv/Ev, IFNAR1−/−, and TD mice following infection with SB or treatment with IFN-α/β. Candidate effectors of alternative antiviral pathways were those genes induced by virus infection or IFN-α/β treatment in 129 Sv/Ev and TD-derived BMDC but not in virus-infected or IFN-α/β-treated IFNAR1−/− cells. Statistical analyses of gene array data identified 44 genes that met these criteria which are discussed.

scholarly journals Measles Virus N Protein Inhibits Host Translation by Binding to eIF3-p40

2007 ◽  
Vol 81 (21) ◽  
pp. 11569-11576 ◽  
Author(s):  
Hiroki Sato ◽  
Munemitsu Masuda ◽  
Moeko Kanai ◽  
Kyoko Tsukiyama-Kohara ◽  
Misako Yoneda ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mammalian Cells ◽  
Measles Virus ◽  
Encephalomyocarditis Virus ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Translation System ◽  
Dependent Manner ◽  
Initiation Factors ◽  
Human T Cell

ABSTRACT The nonsegmented, negative-sense RNA genome of measles virus (MV) is encapsidated by the virus-encoded nucleocapsid protein (N). In this study, we searched for N-binding cellular proteins by using MV-N as bait and screening the human T-cell cDNA library by yeast two-hybrid assay and isolated the p40 subunit of eukaryotic initiation factor 3 (eIF3-p40) as a binding partner. The interaction between MV-N and eIF3-p40 in mammalian cells was confirmed by coimmunoprecipitation. Since eIF3-p40 is a translation initiation factor, we analyzed the potential inhibitory effect of MV-N on protein synthesis. Glutathione S-transferase (GST)-fused MV-N (GST-N) inhibited translation of reporter mRNAs in rabbit reticulocyte lysate translation system in a dose-dependent manner. Encephalomyocarditis virus internal ribosomal entry site-mediated translation, which requires canonical initiation factors to initiate translation, was also inhibited by GST-N. In contrast, a unique form of translation mediated by the intergenic region of Plautia stali intestine virus, which can assemble 80S ribosomes in the absence of canonical initiation factors, was scarcely affected by GST-N. In vivo expression of MV-N induced by the Cre/loxP switching system inhibited the synthesis of a transfected reporter protein, as well as overall protein synthesis. These results suggest that MV-N targets eIF3-p40 and may be involved in inhibiting MV-induced host translation.

scholarly journals Zika virus infection differentially affects genome-wide transcription in neuronal cells and myeloid dendritic cells

PLoS ONE ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. e0231049
Author(s):  
Tamina Park ◽  
Myung-gyun Kang ◽  
Seung-hwa Baek ◽  
Chang Hoon Lee ◽  
Daeui Park
Keyword(s):  
Dendritic Cells ◽  
Virus Infection ◽  
Zika Virus ◽  
Neuronal Cells ◽  
Myeloid Dendritic Cells ◽  
Zika Virus Infection ◽  
Genome Wide

scholarly journals Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection

2004 ◽  
Vol 5 (12) ◽  
pp. 1227-1234 ◽  
Author(s):  
Elina I Zuniga ◽  
Dorian B McGavern ◽  
Jose L Pruneda-Paz ◽  
Chao Teng ◽  
Michael B A Oldstone
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Virus Infection ◽  
Plasmacytoid Dendritic Cells ◽  
Myeloid Dendritic Cells

scholarly journals Resistance to Vesicular Stomatitis Virus Infection Requires a Functional Cross Talk between the Eukaryotic Translation Initiation Factor 2α Kinases PERK and PKR

2004 ◽  
Vol 78 (23) ◽  
pp. 12747-12761 ◽  
Author(s):  
Dionissios Baltzis ◽  
Li-Ke Qu ◽  
Stavroula Papadopoulou ◽  
Jaime D. Blais ◽  
John C. Bell ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Virus Infection ◽  
Vesicular Stomatitis Virus ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation ◽  
Vesicular Stomatitis ◽  
Eif2α Kinase

ABSTRACT Phosphorylation of the alpha (α) subunit of the eukaryotic translation initiation factor 2 (eIF2) leads to the inhibition of protein synthesis in response to diverse stress conditions, including viral infection. The eIF2α kinase PKR has been shown to play an essential role against vesicular stomatitis virus (VSV) infection. We demonstrate here that another eIF2α kinase, the endoplasmic reticulum-resident protein kinase PERK, contributes to cellular resistance to VSV infection. We demonstrate that mouse embryonic fibroblasts (MEFs) from PERK−/− mice are more susceptible to VSV-mediated apoptosis than PERK+/+ MEFs. The higher replication capacity of VSV in PERK−/− MEFs results from their inability to attenuate viral protein synthesis due to an impaired eIF2α phosphorylation. We also show that VSV-infected PERK−/− MEFs are unable to fully activate PKR, suggesting a cross talk between the two eIF2α kinases in virus-infected cells. These findings further implicate PERK in virus infection, and provide evidence that the antiviral and antiapoptotic roles of PERK are mediated, at least in part, via the activation of PKR.

scholarly journals Novel Human Tenascin-C Function-Blocking Camel Single Domain Nanobodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Sayda Dhaouadi ◽  
Rahma Ben Abderrazek ◽  
Thomas Loustau ◽  
Chérine Abou-Faycal ◽  
Ayoub Ksouri ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dendritic Cells ◽  
Mesangial Cells ◽  
Single Domain ◽  
Myeloid Dendritic Cells ◽  
Electron Microscopic ◽  
Microscopic Imaging ◽  
Tenascin C ◽  
Fibronectin Type Iii ◽  
Fibronectin Type

The extracellular matrix (ECM) molecule Tenascin-C (TNC) is well-known to promote tumor progression by multiple mechanisms. However, reliable TNC detection in tissues of tumor banks remains limited. Therefore, we generated dromedary single-domain nanobodies Nb3 and Nb4 highly specific for human TNC (hTNC) and characterized the interaction with TNC by several approaches including ELISA, western blot, isothermal fluorescence titration and negative electron microscopic imaging. Our results revealed binding of both nanobodies to distinct sequences within fibronectin type III repeats of hTNC. By immunofluroescence and immunohistochemical imaging we observed that both nanobodies detected TNC expression in PFA and paraffin embedded human tissue from ulcerative colitis, solid tumors and liver metastasis. As TNC impairs cell adhesion to fibronectin we determined whether the nanobodies abolished this TNC function. Indeed, Nb3 and Nb4 restored adhesion of tumor and mesangial cells on a fibronectin/TNC substratum. We recently showed that TNC orchestrates the immune-suppressive tumor microenvironment involving chemoretention, causing tethering of CD11c+ myeloid/dendritic cells in the stroma. Here, we document that immobilization of DC2.4 dendritic cells by a CCL21 adsorbed TNC substratum was blocked by both nanobodies. Altogether, our novel TNC specific nanobodies could offer valuable tools for detection of TNC in the clinical practice and may be useful to inhibit the immune-suppressive and other functions of TNC in cancer and other diseases.

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