scholarly journals Necrosis Pancreatic Infectious Virus does not block 701-STAT1 (α/β) tyrosine in Oncorhynchus mykiss (‎Salmoniformes: ‎Salmonidae).

2020 ◽  
Vol 22 (2) ◽  
pp. 1-11
Author(s):  
Donald Arguedas Cortés
Keyword(s):  
Oncorhynchus Mykiss ◽  
Signaling Pathway ◽  
Infectious Virus ◽  
Nuclear Translocation ◽  
Infectious Pancreatic Necrosis Virus ◽  
Type I ◽  
Interferon Stimulated Genes ◽  
Infected Cells ◽  
Pancreatic Necrosis Virus ◽  
The Relationship

ABSTRACT: Necrosis Pancreatic Infectious Virus does not block 701-STAT1 (α/β) tyrosine in Oncorhynchus mykiss (‎Salmoniformes: ‎Salmonidae). Introduction: Infectious pancreatic necrosis virus (IPNV) is a pathogen important that affects predominantly salmonids. The type I interferon alpha system has a crucial role in the first line of defense against IPNV infection. IFN-I(α) activation triggers the signaling pathway JAK-STAT, binding to their receptors results in the rapid phosphorylation of STATs a critical step for the nuclear translocation to induce the interferon stimulated genes (ISGs). The relationship between infectivity level of IPNV strain and pathway signaling of IFN is yet poorly understood. Objective: our purpose was to investigate if the IFN-I(α) signaling pathway is affected by IPNV strains of different infectivity levels. Methods: We used two IPNV isolated (VR-299 and Sp) to infect RTG-2 cells. Total RNA was isolated using the commercial kit for determine to VP2 expression and ISGs using qRT-PCR. Western Immunoblotting analysis was carried out for determine the 701 STAT1(α/β) phosphorylation into infected cells. Results: Hence, a higher virulence strain is not associated with a greater blocking effect for interferon signaling. Furthermore, the activation of Y701-STAT1 (α/β) was significantly increased in serotype Sp virus infected cells compared with serotype VR-299 virus infected cells, indicating that IPNV inhibits IFN signaling pathway. Conclusions: As concluded, IPNV does not block the phosphorylation of 701-tyrosine STAT1 (α/β) stimulated by IFN-I(α), contrary to other RNA viruses.

scholarly journals Porcine Reproductive and Respiratory Syndrome Virus Inhibits Type I Interferon Signaling by Blocking STAT1/STAT2 Nuclear Translocation

2010 ◽  
Vol 84 (21) ◽  
pp. 11045-11055 ◽  
Author(s):  
Deendayal Patel ◽  
Yuchen Nan ◽  
Meiyan Shen ◽  
Krit Ritthipichai ◽  
Xiaoping Zhu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Viral Infections ◽  
Nuclear Translocation ◽  
Type I Interferons ◽  
Respiratory Syndrome Virus ◽  
Detectable Effect ◽  
Type I ◽  
Live Virus ◽  
Type I Ifns ◽  
Infected Cells

ABSTRACT Type I interferons (IFNs) IFN-α/β play an important role in innate immunity against viral infections by inducing antiviral responses. Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits the synthesis of type I IFNs. However, whether PRRSV can inhibit IFN signaling is less well understood. In the present study, we found that PRRSV interferes with the IFN signaling pathway. The transcript levels of IFN-stimulated genes ISG15 and ISG56 and protein level of signal transducer and activator of transcription 2 (STAT2) in PRRSV VR2385-infected MARC-145 cells were significantly lower than those in mock-infected cells after IFN-α treatment. IFN-induced phosphorylation of both STAT1 and STAT2 and their heterodimer formation in the PRRSV-infected cells were not affected. However, the majority of the STAT1/STAT2/IRF9 (IFN regulatory factor 9) heterotrimers remained in the cytoplasm of PRRSV-infected cells, which indicates that the nuclear translocation of the heterotrimers was blocked. Overexpression of NSP1β of PRRSV VR2385 inhibited expression of ISG15 and ISG56 and blocked nuclear translocation of STAT1, which suggests that NSP1β might be the viral protein responsible for the inhibition of IFN signaling. PRRSV infection in primary porcine pulmonary alveolar macrophages (PAMs) also inhibited IFN-α-stimulated expression of the ISGs and the STAT2 protein. In contrast, a licensed low-virulence vaccine strain, Ingelvac PRRS modified live virus (MLV), activated expression of IFN-inducible genes, including those of chemokines and antiviral proteins, in PAMs without the addition of external IFN and had no detectable effect on IFN signaling. These findings suggest that PRRSV interferes with the activation and signaling pathway of type I IFNs by blocking ISG factor 3 (ISGF3) nuclear translocation.

scholarly journals Rotavirus inhibits IFN-induced STAT nuclear translocation by a mechanism that acts after STAT binding to importin-α

2014 ◽  
Vol 95 (8) ◽  
pp. 1723-1733 ◽  
Author(s):  
Gavan Holloway ◽  
Vi T. Dang ◽  
David A. Jans ◽  
Barbara S. Coulson
Keyword(s):  
Nuclear Export ◽  
Nuclear Translocation ◽  
Strain Analysis ◽  
Nuclear Accumulation ◽  
Type I ◽  
Group A Rotaviruses ◽  
Importin Α ◽  
Group A ◽  
Infected Cells ◽  
Novel Strategy

The importance of innate immunity to rotaviruses is exemplified by the range of strategies evolved by rotaviruses to interfere with the IFN response. We showed previously that rotaviruses block gene expression induced by type I and II IFNs, through a mechanism allowing activation of signal transducer and activator of transcription (STAT) 1 and STAT2 but preventing their nuclear accumulation. This normally occurs through activated STAT1/2 dimerization, enabling an interaction with importin α5 that mediates transport into the nucleus. In rotavirus-infected cells, STAT1/2 inhibition may limit the antiviral actions of IFN produced early in infection. Here we further analysed the block to STAT1/2 nuclear accumulation, showing that activated STAT1 accumulates in the cytoplasm in rotavirus-infected cells. STAT1/2 nuclear accumulation was inhibited by rotavirus even in the presence of the nuclear export inhibitor Leptomycin B, demonstrating that enhanced nuclear export is not involved in STAT1/2 cytoplasmic retention. The ability to inhibit STAT nuclear translocation was completely conserved amongst the group A rotaviruses tested, including a divergent avian strain. Analysis of mutant rotaviruses indicated that residues after amino acid 47 of NSP1 are dispensable for STAT inhibition. Furthermore, expression of any of the 12 Rhesus monkey rotavirus proteins did not inhibit IFN-stimulated STAT1 nuclear translocation. Finally, co-immunoprecipitation experiments from transfected epithelial cells showed that STAT1/2 binds importin α5 normally following rotavirus infection. These findings demonstrate that rotavirus probably employs a novel strategy to inhibit IFN-induced STAT signalling, which acts after STAT activation and binding to the nuclear import machinery.

scholarly journals Interplay of Signal Mediators of Decapentaplegic (Dpp): Molecular Characterization of Mothers against dpp, Medea, and Daughters against dpp

1998 ◽  
Vol 9 (8) ◽  
pp. 2145-2156 ◽  
Author(s):  
Hirofumi Inoue ◽  
Takeshi Imamura ◽  
Yasuhiro Ishidou ◽  
Masao Takase ◽  
Yoshiyuki Udagawa ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Characterization ◽  
Intracellular Signaling ◽  
Essential Role ◽  
Nuclear Translocation ◽  
Type I ◽  
Smad Proteins ◽  
Signal Mediators

Decapentaplegic (Dpp) plays an essential role inDrosophila development, and analyses of the Dpp signaling pathway have contributed greatly to understanding of the actions of the TGF-β superfamily. Intracellular signaling of the TGF-β superfamily is mediated by Smad proteins, which are now grouped into three classes. Two Smads have been identified inDrosophila. Mothers against dpp (Mad) is a pathway-specific Smad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetically shown to antagonize Dpp signaling. Here we report the identification of a common mediator Smad inDrosophila, which is closely related to human Smad4. Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. Dad stably associates with Tkv and thereby inhibits Tkv-induced Mad phosphorylation. Dad also blocks hetero-oligomerization and nuclear translocation of Mad. We also show that Mad exists as a monomer in the absence of Tkv stimulation. Tkv induces homo-oligomerization of Mad, and Dad inhibits this step. Finally, we propose a model for Dpp signaling by Drosophila Smad proteins.

scholarly journals Murine Coronavirus Delays Expression of a Subset of Interferon-Stimulated Genes

2010 ◽  
Vol 84 (11) ◽  
pp. 5656-5669 ◽  
Author(s):  
Kristine M. Rose ◽  
Ruth Elliott ◽  
Luis Martínez-Sobrido ◽  
Adolfo García-Sastre ◽  
Susan R. Weiss
Keyword(s):  
Sindbis Virus ◽  
Sendai Virus ◽  
Hepatitis Virus ◽  
Type I ◽  
Interferon Stimulated Genes ◽  
A Cell ◽  
Infected Cells ◽  
Ifn Treatment ◽  
Β Receptor ◽  
Murine Coronavirus

ABSTRACT The importance of the type I interferon (IFN-I) system in limiting coronavirus replication and dissemination has been unequivocally demonstrated by rapid lethality following infection of mice lacking the alpha/beta IFN (IFN-α/β) receptor with mouse hepatitis virus (MHV), a murine coronavirus. Interestingly, MHV has a cell-type-dependent ability to resist the antiviral effects of IFN-α/β. In primary bone-marrow-derived macrophages and mouse embryonic fibroblasts, MHV replication was significantly reduced by the IFN-α/β-induced antiviral state, whereas IFN treatment of cell lines (L2 and 293T) has only minor effects on replication (K. M. Rose and S. R. Weiss, Viruses 1:689-712, 2009). Replication of other RNA viruses, including Theiler's murine encephalitis virus (TMEV), vesicular stomatitis virus (VSV), Sindbis virus, Newcastle disease virus (NDV), and Sendai virus (SeV), was significantly inhibited in L2 cells treated with IFN-α/β, and MHV had the ability to rescue only SeV replication. We present evidence that MHV infection can delay interferon-stimulated gene (ISG) induction mediated by both SeV and IFN-β but only when MHV infection precedes SeV or IFN-β exposure. Curiously, we observed no block in the well-defined IFN-β signaling pathway that leads to STAT1-STAT2 phosphorylation and translocation to the nucleus in cultures infected with MHV. This observation suggests that MHV must inhibit an alternative IFN-induced pathway that is essential for early induction of ISGs. The ability of MHV to delay SeV-mediated ISG production may partially involve limiting the ability of IFN regulatory factor 3 (IRF-3) to function as a transcription factor. Transcription from an IRF-3-responsive promoter was partially inhibited by MHV; however, IRF-3 was transported to the nucleus and bound DNA in MHV-infected cells superinfected with SeV.

scholarly journals HIV-1 infection of human macrophages directly induces viperin which inhibits viral production

Blood ◽  
2012 ◽  
Vol 120 (4) ◽  
pp. 778-788 ◽  
Author(s):  
Najla Nasr ◽  
Susan Maddocks ◽  
Stuart G. Turville ◽  
Andrew N. Harman ◽  
Natalie Woolger ◽  
...  
Keyword(s):  
T Cells ◽  
Nuclear Translocation ◽  
Target Cells ◽  
Type I ◽  
Viral Production ◽  
Protein Prenylation ◽  
Interferon Stimulated Genes ◽  
Interferon Induction ◽  
Adenosyl Methionine ◽  
Hiv 1

AbstractMacrophages are key target cells for HIV-1. HIV-1BaL induced a subset of interferon-stimulated genes in monocyte-derived macrophages (MDMs), which differed from that in monocyte-derived dendritic cells and CD4 T cells, without inducing any interferons. Inhibition of type I interferon induction was mediated by HIV-1 inhibition of interferon-regulated factor (IRF3) nuclear translocation. In MDMs, viperin was the most up-regulated interferon-stimulated genes, and it significantly inhibited HIV-1 production. HIV-1 infection disrupted lipid rafts via viperin induction and redistributed viperin to CD81 compartments, the site of HIV-1 egress by budding in MDMs. Exogenous farnesol, which enhances membrane protein prenylation, reversed viperin-mediated inhibition of HIV-1 production. Mutagenesis analysis in transfected cell lines showed that the internal S-adenosyl methionine domains of viperin were essential for its antiviral activity. Thus viperin may contribute to persistent noncytopathic HIV-1 infection of macrophages and possibly to biologic differences with HIV-1–infected T cells.

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