scholarly journals ZMPSTE24 defends against influenza and other pathogenic viruses

2017 ◽  
Vol 214 (4) ◽  
pp. 919-929 ◽  
Author(s):  
Bishi Fu ◽  
Lingyan Wang ◽  
Shitao Li ◽  
Martin E. Dorf
Keyword(s):  
Viral Entry ◽  
Influenza A ◽  
Defense Mechanisms ◽  
Transmembrane Protein ◽  
Influenza Infection ◽  
In Vivo Studies ◽  
Antiviral Protein ◽  
Dna Viruses ◽  
Specific Effector

Zinc metallopeptidase STE24 (ZMPSTE24) is a transmembrane metalloprotease whose catalytic activity is critical for processing lamin A on the inner nuclear membrane and clearing clogged translocons on the endoplasmic reticulum. We now report ZMPSTE24 is a virus-specific effector that restricts enveloped RNA and DNA viruses, including influenza A, Zika, Ebola, Sindbis, vesicular stomatitis, cowpox, and vaccinia, but not murine leukemia or adenovirus. ZMPSTE24-mediated antiviral action is independent of protease activity. Coimmunoprecipitation studies indicate ZMPSTE24 can complex with proteins of the interferon-induced transmembrane protein (IFITM) family. IFITM proteins impede viral entry, and ZMPSTE24 expression is necessary for IFITM antiviral activity. In vivo studies demonstrate ZMPSTE24-deficient mice display higher viral burdens, enhanced cytokine production, and increased mortality after influenza infection. Collectively, these findings identify ZMPSTE24 as an intrinsic broad-spectrum antiviral protein and provide insights into antiviral defense mechanisms.

scholarly journals Direct Interactions between Calcitonin-Like Receptor (CLR) and CGRP-Receptor Component Protein (RCP) Regulate CGRP Receptor Signaling

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1850-1860 ◽  
Author(s):  
Sophie C. Egea ◽  
Ian M. Dickerson
Keyword(s):  
Cell Surface ◽  
Transmembrane Protein ◽  
Direct Interaction ◽  
Dominant Negative ◽  
In Vivo Studies ◽  
Cgrp Receptor ◽  
Receptor Component ◽  
Soluble Fusion Protein ◽  
Component Protein

Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates with CLR signaling and CGRP efficacy. It is not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it coimmunoprecipitated with RCP and inhibited signaling from endogenous CLR. Expression of this dominant-negative domain of CLR did not significantly inhibit trafficking of CLR to the cell surface, and thus RCP may not have a chaperone function for CLR. Instead, RCP may regulate CLR signaling in the cell membrane, and direct interaction between RCP and CLR is required for CLR activation. To date, RCP has been found to interact only with CLR and represents a novel neuroendocrine regulatory step in GPCR signaling.

Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies

2001 ◽  
Vol 52 (1) ◽  
pp. 43-53 ◽  
Author(s):  
A Horváth ◽  
I Andersen ◽  
K Junker ◽  
B Lyck Fogh-Schultz ◽  
E Holm Nielsen ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
In Vivo Studies ◽  
Virus Infections ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid P

IFITM3 rs12252 T>C polymorphism is associated with the risk of severe influenza: a meta-analysis

2015 ◽  
Vol 143 (14) ◽  
pp. 2975-2984 ◽  
Author(s):  
Y. XUAN ◽  
L. N. WANG ◽  
W. LI ◽  
H. R. ZI ◽  
Y. GUO ◽  
...  
Keyword(s):  
Influenza A ◽  
Web Of Science ◽  
Transmembrane Protein ◽  
Influenza Infection ◽  
Meta Analysis ◽  
Severe Illness ◽  
Severe Influenza ◽  
Increased Risk ◽  
Interferon Pathway ◽  
Comprehensive Literature Search

SUMMARYThe interferon-inducible transmembrane protein 3 (IFITM3), as one of the key genes involved in the interferon pathway, is critical for defending the host against influenza virus, and the rs12252 T>C variant in IFITM3 might be associated with susceptibility to severe influenza. Owing to contradictory and inconclusive results, we performed a meta-analysis to assess the association between rs12252 T>C polymorphism and severe influenza risk. A comprehensive literature search up to 1 August 2014 was conducted in EMBASE, Pubmed, Web of Science, VIP, Wanfang and CNKI databases. Four eligible studies with a total of 445 influenza patients and 3396 controls were included in this meta-analysis. Overall, our results demonstrated a significant association between the IFITM3 rs12252 T>C polymorphism and influenza risk [C vs. T: odds ratio (OR) 1·68, 95% confidence interval (CI) 1·32–2·13; CC vs. CT+TT: OR 2·38, 95% CI 1·52–3·73; CC+CT vs. TT: OR 1·62, 95% CI 1·18–2·22]. Stratification by ethnicity indicated that the variant C allele was associated with an 88% increased risk of influenza in Asians (C vs. T: OR 1·88, 95% CI 1·34–2·62). Moreover, subjects carrying the variant C allele had an increased risk of developing severe illness upon influenza infection (C vs. T: OR 2·70, 95% CI 1·86–3·94). However, no significant association was observed in patients with mild infection (C vs. T: OR 1·26, 95% CI 0·93–1·71). Our meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is significantly associated with increased risk of severe influenza but not with the chance of initial virus infection.

scholarly journals A Novel Sulfonated Derivative of β-Cyclodextrin Effectively Inhibits Influenza A Virus Infection in vitro and in vivo

Acta Naturae ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 20-30 ◽  
Author(s):  
E. P. Goncharova ◽  
Y. A. Kostyro ◽  
A. V. Ivanov ◽  
M. A. Zenkova
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
High Efficiency ◽  
Influenza Infection ◽  
Lethal Infection ◽  
Novel Drugs ◽  
Infected Cells ◽  
Low Toxicity

The development of novel drugs against the influenza virus with high efficiency and low toxicity is an urgent and important task. Previous reports have demonstrated that compounds based on sulfo derivatives of oligo- and polysaccharides possess high antiviral activity. In this study, we have examined the ability of a novel sulfonated derivative of -cyclodextrin (KS-6469) to inhibit the influenza virus A/WSN/33 (H1N1) infection in vitro and in vivo. The antiviral potential of KS-6469 against the influenza virus was evaluated in Madin-Darby Canine Kidney epithelial cells treated with serially diluted KS-6469. We found out that KS-6469 completely inhibited viral reproduction after treatment of the infected cells with the compound for 48 h. Our data show that double intranasal treatment of mice with KS-6469 fully protected the animals from a lethal infection and significantly decreased the viral titers in the lungs of the infected animals. Thus, the novel sulfonated -cyclodextrin derivative KS-6469 is a promising candidate for the development of antiviral drugs for preventing and treating the influenza infection.

scholarly journals TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

2020 ◽  
Vol 11 (12) ◽  
pp. 894-914
Author(s):  
Nan Sun ◽  
Li Jiang ◽  
Miaomiao Ye ◽  
Yihan Wang ◽  
Guangwen Wang ◽  
...  
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Influenza Infection ◽  
Type I ◽  
Subsequent Formation ◽  
Antiviral Immune Response ◽  
Signaling Complex ◽  
Deficient Mice

AbstractTripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.

scholarly journals Natural Nrf2 Activators from Juices, Wines, Coffee, and Cocoa

Beverages ◽  
2020 ◽  
Vol 6 (4) ◽  
pp. 68
Author(s):  
Mallique Qader ◽  
Jian Xu ◽  
Yuejun Yang ◽  
Yuancai Liu ◽  
Shugeng Cao
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Target Genes ◽  
Antioxidant Activities ◽  
Reactive Oxygen ◽  
Polyphenolic Compounds ◽  
Cellular Systems ◽  
In Vivo Studies

Juices, wine, coffee, and cocoa are rich sources of natural polyphenolic compounds that have potent antioxidant activities proven by in vitro and in vivo studies. These polyphenolic compounds quench reactive oxygen and nitrogen species (RONS) or reactive free radicals and act as natural antioxidants which are also able to protect against reactive oxygen species (ROS)-mediated oxidative damage, which elevates cellular antioxidant capacity to induce antioxidant defense mechanisms by modulating transcription factors. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor encoded in humans. It is activated as a result of oxidative stress and induces the expression of its target genes. This is one of the most important cellular defense mechanisms against oxidative stress. However, the oxidative stress alone is not enough to activate Nrf2. Hence phytochemicals, especially polyphenolics, act as natural Nrf2 activators. Herein, this review discusses the natural products identified in juices, coffee, cocoa and wines that modulate Nrf2 activity in cellular systems.

scholarly journals Upper respiratory tract infection in children – immunostimulating treatment

2021 ◽  
Vol 11 (9) ◽  
pp. 80-89
Author(s):  
Dariusz Kaczmarczyk ◽  
Dawid Zagacki ◽  
Alina Morawiec-Sztandera
Keyword(s):  
Defense Mechanisms ◽  
Viral Infections ◽  
Medical Product ◽  
In Vivo Studies ◽  
Upper Respiratory Tract ◽  
Inosine Pranobex ◽  
Upper Respiratory ◽  
Cellular And Humoral Immunity

This paper is a review of publications on viral infections of the upper aerotract in children. Recurring infections can be a consequence of the lack of treatment, inappropriate therapy or accompanying diseases. It is possible that an impaired condition of immunity leads to recurring infections. In this review a great deal of attention has been given to the mechanisms and the various stages of viral infection, and the onset of an organism’s defense mechanisms against viruses. The function of the immunomodulatory and immunostimulatory medical product, namely inosine pranobex has been evaluated in in vitro and in vivo studies. A review of the antiviral activity of inosine pranobex and the onset of cellular and humoral immunity has been presented.

The In Vivo Source of Type I and Type III IFNs is Pathogen Dependent

2021 ◽  
Author(s):  
Marvin J. Sandoval ◽  
Hsiang-Chi Tseng ◽  
Heidi P. Risman ◽  
Sergey Smirnov ◽  
Qing Li ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Virus Infection ◽  
Respiratory Tract ◽  
Influenza A ◽  
Influenza Infection ◽  
Type I ◽  
Protective Effects ◽  
Type Iii

Type I (-α, β) and type III (-λ) interferons (IFNs) are produced in response to virus infection and upregulate a largely overlapping set of IFN stimulated genes which mediate the protective effects of these antiviral cytokines. In vitro studies have demonstrated the redundancy of these two cytokine families which activate the same transcription factor, IFN stimulated gene factor 3 (ISGF3), via distinct ligands and receptors. However, in vivo, these IFN types do have distinct functions based on receptor distribution, but also ligand availability. Using a newly generated IFN-λ reporter mouse strain we have observed that both type I and type III IFNs are produced in response to respiratory tract infection by Newcastle disease virus (NDV) and influenza A virus (IAV). In the case of NDV these IFNs are synthesized by different cell types. Type I IFNs are produced primarily by alveolar macrophages, type III IFNs are made only by epithelial cells, and production of either is dependent on MAVS. While epithelial cells of the respiratory tract represent the primary target of IAV infection, we found that they did not significantly contribute to IFN-λ production, and IFN-λ protein levels were largely unaffected in the absence of MAVS. Instead we found that pDCs, a cell type known for robust IFN-α production via TLR/MyD88 signaling, were the major producers of IFN-λ during IAV infection, with pDC depletion during influenza infection resulting in significantly reduced levels of both IFN-α and IFN-λ. In addition, we were able to demonstrate that pDCs rely on type I IFN for optimal IFN-λ production. These studies therefore demonstrate that the in vivo producers of Type III IFNs in response to respiratory virus infection are pathogen dependent, a finding which may explain the varying levels of cytokine production induced by different viral pathogens.

scholarly journals Replication-Competent Influenza A and B Viruses Expressing a Fluorescent Dynamic Timer Protein for In Vitro and In Vivo Studies

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0147723 ◽  
Author(s):  
Michael Breen ◽  
Aitor Nogales ◽  
Steven F. Baker ◽  
Daniel R. Perez ◽  
Luis Martínez-Sobrido
Keyword(s):  
Influenza A ◽  
In Vivo Studies
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