scholarly journals The evolution of interferon-tau

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F1-F10 ◽  
Author(s):  
Alan D Ealy ◽  
Lydia K Wooldridge
Keyword(s):  
Biological Activity ◽  
Molecular Cloning ◽  
Type I Interferon ◽  
Cdna Libraries ◽  
Type I ◽  
Interferon Tau ◽  
Sheep And Goats ◽  
Type I Ifns

Thirty years ago, a novel type I interferon (IFN) was identified by molecular cloning of cDNA libraries constructed from RNA extracted from ovine and bovine pre-implantation embryos. This protein was eventually designated as IFN-tau (IFNT) to highlight its trophoblast-dependent expression. IFNT function is not immune related. Instead, it interacts with the maternal system to initiate the establishment and maintenance of pregnancy. This activity is indispensable for the continuation of pregnancy. Our review will describe how IFNT evolved from other type I IFNs to function in this new capacity. IFNT genes have only been identified in pecoran ruminants within the Artiodactyla order (e.g. cattle, sheep, goats, deer, antelope, giraffe). The ancestral IFNT gene emerged approximately 36 million years ago most likely from rearrangement and/or insertion events that combined an ancestral IFN-omega (IFNW) gene with a trophoblast-specifying promoter/enhancer. Since then, IFNT genes have duplicated, likely through conversion events, and mutations have allowed them to adapt to their new function in concert with the emergence of different species. Multiple IFNT polymorphisms have been identified in cattle, sheep and goats. These genes and gene alleles encode proteins that do not display identical antiviral, antiproliferative and antiluteolytic activities. The need for multiple IFNT genes, numerous alleles and distinct activities remains debatable, but the consensus is that this complexity in IFNT expression and biological activity must be needed to provide the best opportunity for pregnancy to be recognized by the maternal system so that gestation may continue.

scholarly journals Hemagglutinin of Influenza A Virus Antagonizes Type I Interferon (IFN) Responses by Inducing Degradation of Type I IFN Receptor 1

2015 ◽  
Vol 90 (5) ◽  
pp. 2403-2417 ◽  
Author(s):  
Chuan Xia ◽  
Madhuvanthi Vijayan ◽  
Curtis J. Pritzl ◽  
Serge Y. Fuchs ◽  
Adrian B. McDermott ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Influenza A Virus ◽  
Influenza A ◽  
Type I Interferon ◽  
Innate Immune ◽  
Host Cells ◽  
Type I ◽  
Type I Ifn ◽  
Type I Ifns ◽  
Ha Protein

ABSTRACTInfluenza A virus (IAV) employs diverse strategies to circumvent type I interferon (IFN) responses, particularly by inhibiting the synthesis of type I IFNs. However, it is poorly understood if and how IAV regulates the type I IFN receptor (IFNAR)-mediated signaling mode. In this study, we demonstrate that IAV induces the degradation of IFNAR subunit 1 (IFNAR1) to attenuate the type I IFN-induced antiviral signaling pathway. Following infection, the level of IFNAR1 protein, but not mRNA, decreased. Indeed, IFNAR1 was phosphorylated and ubiquitinated by IAV infection, which resulted in IFNAR1 elimination. The transiently overexpressed IFNAR1 displayed antiviral activity by inhibiting virus replication. Importantly, the hemagglutinin (HA) protein of IAV was proved to trigger the ubiquitination of IFNAR1, diminishing the levels of IFNAR1. Further, influenza A viral HA1 subunit, but not HA2 subunit, downregulated IFNAR1. However, viral HA-mediated degradation of IFNAR1 was not caused by the endoplasmic reticulum (ER) stress response. IAV HA robustly reduced cellular sensitivity to type I IFNs, suppressing the activation of STAT1/STAT2 and induction of IFN-stimulated antiviral proteins. Taken together, our findings suggest that IAV HA causes IFNAR1 degradation, which in turn helps the virus escape the powerful innate immune system. Thus, the research elucidated an influenza viral mechanism for eluding the IFNAR signaling pathway, which could provide new insights into the interplay between influenza virus and host innate immunity.IMPORTANCEInfluenza A virus (IAV) infection causes significant morbidity and mortality worldwide and remains a major health concern. When triggered by influenza viral infection, host cells produce type I interferon (IFN) to block viral replication. Although IAV was shown to have diverse strategies to evade this powerful, IFN-mediated antiviral response, it is not well-defined if IAV manipulates the IFN receptor-mediated signaling pathway. Here, we uncovered that influenza viral hemagglutinin (HA) protein causes the degradation of type I IFN receptor subunit 1 (IFNAR1). HA promoted phosphorylation and polyubiquitination of IFNAR1, which facilitated the degradation of this receptor. The HA-mediated elimination of IFNAR1 notably decreased the cells' sensitivities to type I IFNs, as demonstrated by the diminished expression of IFN-induced antiviral genes. This discovery could help us understand how IAV regulates the host innate immune response to create an environment optimized for viral survival in host cells.

Molecular cloning and functional characterization of two duplicated two-cysteine containing type I interferon genes in rock bream Oplegnathus fasciatus

2012 ◽  
Vol 33 (4) ◽  
pp. 886-898 ◽  
Author(s):  
Qiang Wan ◽  
W.D. Niroshana Wicramaarachchi ◽  
Ilson Whang ◽  
Bong-Soo Lim ◽  
Myung-Joo Oh ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Type I Interferon ◽  
Functional Characterization ◽  
Type I ◽  
Oplegnathus Fasciatus ◽  
Rock Bream

scholarly journals Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice

2020 ◽  
Author(s):  
Alexandra I. Wells ◽  
Kalena A. Grimes ◽  
Kenneth Kim ◽  
Emilie Branche ◽  
Christopher J. Bakkenist ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Neurological Complications ◽  
Host Factors ◽  
Type I ◽  
Interferon Signaling ◽  
Systemic Immune Response ◽  
Severe Hepatitis ◽  
Host Determinants ◽  
Type I Ifns

AbstractNeonatal echovirus infections are characterized by severe hepatitis and neurological complications that can be fatal. Here, we show that expression of the human homologue of the neonatal Fc receptor (hFcRn), the primary receptor for echoviruses, and ablation of type I interferon (IFN) signaling are key host determinants involved in echovirus pathogenesis. We show that expression of hFcRn alone is insufficient to confer susceptibility to echovirus infections in mice. However, expression of hFcRn in mice deficient in type I interferon (IFN) signaling, hFcRn-IFNAR−/−, recapitulate the echovirus pathogenesis observed in humans. Luminex-based multianalyte profiling from E11 infected hFcRn-IFNAR−/− mice revealed a robust systemic immune response to infection, including the induction of type I IFNs. Furthermore, similar to the severe hepatitis observed in humans, E11 infection in hFcRn-IFNAR−/− mice caused profound liver damage. Our findings define the host factors involved in echovirus pathogenesis and establish in vivo models that recapitulate echovirus disease.

scholarly journals Bovine Interferon-Tau Activates Type I interferon-Associated Janus-signal Transducer in HPV16-positive Tumor Cell

2020 ◽  
Vol 11 (16) ◽  
pp. 4754-4761
Author(s):  
Geny Fierros-Zárate ◽  
Clarita Olvera ◽  
Gustavo Salazar-Guerrero ◽  
Ausencio Morales-Ortega ◽  
Fernando Reyna ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Type I Interferon ◽  
Type I ◽  
Signal Transducer ◽  
Interferon Tau ◽  
Positive Tumor Cell

ALL-associated JAK1 mutations confer hypersensitivity to the antiproliferative effect of type I interferon

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3287-3295 ◽  
Author(s):  
Tekla Hornakova ◽  
Sabina Chiaretti ◽  
Muriel M. Lemaire ◽  
Robin Foà ◽  
Raouf Ben Abdelali ◽  
...  
Keyword(s):  
Cell Lines ◽  
Type I Interferon ◽  
Type I ◽  
Type I Ifn ◽  
Transcriptional Signature ◽  
Activating Mutations ◽  
Type I Ifns ◽  
Antitumorigenic Effect

Abstract Activating mutations in JAK1 have been reported in acute lymphoblastic leukemias (ALLs). In this study, we found a type I interferon (IFN) transcriptional signature in JAK1 mutation-positive human ALL samples. This signature was recapitulated in vitro by the expression of JAK1 mutants in BW5147 and BaF3 hematopoietic cell lines. Binding of JAK1 to the IFN receptor was essential because mutations in the FERM domain abrogated this effect. Beside the constitutive activation of the type I IFN signaling cascade, JAK1 mutations also strongly potentiated the response to IFN in vitro. Typically, the proliferation of cell lines expressing JAK1A634D was abrogated by type I IFNs. Interestingly, we found that different JAK1 mutations differentially potentiate responses to type I IFNs or to interleukin-9, another cytokine using JAK1 to mediate its effects. This suggests that the type of mutation influences the specificity of the effect on distinct cytokine receptor signaling. Finally, we also showed in an in vivo leukemia model that cells expressing JAK1A634D are hypersensitive to the antiproliferative and antitumorigenic effect of type I IFN, suggesting that type I IFNs should be considered as a potential therapy for ALL with JAK1-activating mutations.

scholarly journals Modulation of Type I Interferon System by African Swine Fever Virus

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 361 ◽  
Author(s):  
Elisabetta Razzuoli ◽  
Giulia Franzoni ◽  
Tania Carta ◽  
Susanna Zinellu ◽  
Massimo Amadori ◽  
...  
Keyword(s):  
Type I Interferon ◽  
African Swine Fever Virus ◽  
Statistical Significance ◽  
Expression Patterns ◽  
African Swine Fever ◽  
Fever Virus ◽  
Type I ◽  
Viral Dissemination ◽  
Type I Ifns ◽  
Interferon System

African Swine Fever Virus (ASFV) has tropism for macrophages, which seems to play a crucial role in disease pathogenesis and viral dissemination. Previous studies showed that ASFV developed mechanisms to evade type I interferon (IFN) responses. Hence, we analyzed the ability of ASFV strains of diverse virulence to modulate IFN-β and IFN-α responses. Porcine monocyte-derived macrophages un-activated (moMΦ) or activated with IFN-α (moMΦ + FN-α) were infected with virulent (22653/14) or attenuated (NH/P68) ASFV strains, and expressions of IFN-β and of 17 IFN-α subtypes genes were monitored over time. ASFV strains of diverse virulence induced different panels of IFN genes: infection of moMΦ with either strains caused statistically significant up-regulation of IFN-α3, -α7/11, whereas only attenuated NH/P68 determined statistically significant up-regulation of IFN-α10, -α12, -α13, -α15, -α17, and IFN-β. Infection of activated moMΦ with either strains resulted in up-regulation of IFN-β and many IFN-α subtypes, but statistical significance was found only for IFN-α1, -α10, -α15, -α16, -α17 in response to NH/P68-infection only. These data revealed differences in type I IFNs expression patterns, with differences between strains of diverse virulence. In addition, virulent 22653/14 ASFV seems to have developed mechanisms to suppress the induction of several type I IFN genes.

scholarly journals Type I Interferon Response Limits Astrovirus Replication and Protects against Increased Barrier PermeabilityIn VitroandIn Vivo

2015 ◽  
Vol 90 (4) ◽  
pp. 1988-1996 ◽  
Author(s):  
Shauna A. Marvin ◽  
C. Theodore Huerta ◽  
Bridgett Sharp ◽  
Pamela Freiden ◽  
Troy D. Cline ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Barrier Permeability ◽  
Type I Ifns ◽  
Human Astroviruses ◽  
Human Astrovirus ◽  
New Evidence

ABSTRACTLittle is known about intrinsic epithelial cell responses against astrovirus infection. Here we show that human astrovirus type 1 (HAstV-1) infection induces type I interferon (beta interferon [IFN-β]) production in differentiated Caco2 cells, which not only inhibits viral replication by blocking positive-strand viral RNA and capsid protein synthesis but also protects against HAstV-1-increased barrier permeability. Excitingly, we found similar resultsin vivousing a murine astrovirus (MuAstV) model, providing new evidence that virus-induced type I IFNs may protect against astrovirus replication and pathogenesisin vivo.IMPORTANCEHuman astroviruses are a major cause of pediatric diarrhea, yet little is known about the immune response. Here we show that type I interferon limits astrovirus infection and preserves barrier permeability bothin vitroandin vivo. Importantly, we characterized a new mouse model for studying astrovirus replication and pathogenesis.

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