Faculty Opinions recommendation of Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity.

2017 ◽  
Author(s):  
John Grainger
Keyword(s):  
Innate Immunity ◽  
Respiratory Burst ◽  
Transmembrane Protein

scholarly journals Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity

2017 ◽  
Vol 214 (4) ◽  
pp. 1111-1128 ◽  
Author(s):  
David C. Thomas ◽  
Simon Clare ◽  
John M. Sowerby ◽  
Mercedes Pardo ◽  
Jatinder K. Juss ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Host Defense ◽  
Respiratory Burst ◽  
Transmembrane Protein ◽  
Uncharacterized Protein ◽  
Napdh Oxidase ◽  
Melanoma Metastases ◽  
Membrane Bound ◽  
Severe Immunodeficiency

The phagocyte respiratory burst is crucial for innate immunity. The transfer of electrons to oxygen is mediated by a membrane-bound heterodimer, comprising gp91phox and p22phox subunits. Deficiency of either subunit leads to severe immunodeficiency. We describe Eros (essential for reactive oxygen species), a protein encoded by the previously undefined mouse gene bc017643, and show that it is essential for host defense via the phagocyte NAPDH oxidase. Eros is required for expression of the NADPH oxidase components, gp91phox and p22phox. Consequently, Eros-deficient mice quickly succumb to infection. Eros also contributes to the formation of neutrophil extracellular traps (NETS) and impacts on the immune response to melanoma metastases. Eros is an ortholog of the plant protein Ycf4, which is necessary for expression of proteins of the photosynthetic photosystem 1 complex, itself also an NADPH oxio-reductase. We thus describe the key role of the previously uncharacterized protein Eros in host defense.

LncRNA IFITM4P regulates host antiviral responses by acting as a ceRNA

2021 ◽  
Author(s):  
Meng Xiao ◽  
Yuhai Chen ◽  
Song Wang ◽  
Shasha Liu ◽  
Kul Raj Rai ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Viral Infection ◽  
Noncoding Rna ◽  
Transmembrane Protein ◽  
Family Members ◽  
Ectopic Expression ◽  
Antiviral Immunity ◽  
Mrna Levels ◽  
Antiviral Responses ◽  
Innate Antiviral Immunity

Long noncoding RNAs (lncRNAs) are involved in numerous cellular processes. Increasing evidence suggests that some lncRNAs function in immunity through various complex mechanisms. However, implication of a large fraction of lncRNAs in antiviral innate immunity remains uncharacterized. Here, we identified a lncRNA called lncRNA IFITM4P that was transcribed from interferon induced transmembrane protein 4 pseudogene (IFITM4P) , a pseudogene belonging to interferon induced transmembrane protein (IFITM) family. We found that expression of lncRNA IFITM4P was significantly induced by infection with several viruses including influenza A virus (IAV). Importantly, lncRNA IFITM4P acted as a positive regulator of innate antiviral immunity. Ectopic expression of lncRNA IFITM4P significantly suppressed IAV replication in vitro , whereas IFITM4P deficiency promoted the viral production. We further observed that expression of lncRNA IFITM4P was up-regulated by interferon (IFN) signaling during viral infection, and altering the expression of this lncRNA had significant effects on the mRNA levels of several IFITM family members including IFITM1, IFITM2 and IFITM3. Moreover, it was identified that lncRNA IFITM4P was a target of miR-24-3p that represses mRNA of IFITM1, IFITM2 and IFITM3. The experiments demonstrated that lncRNA IFITM4P was able to cross-regulate the expression of IFITM family members as a competing endogenous RNA (ceRNA), leading to increased stability of these IFITM mRNAs. Together, our results reveal that lncRNA IFITM4P, as a ceRNA, is involved in innate immunity against viral infection through the lncRNA IFITM4P-miR-24-3p- IFITM1/2/3 regulatory network. IMPORTANCE LncRNAs play important roles in various biological processes, but their involvement in host antiviral responses remains largely unknown. In this study, we revealed that the pseudogene IFITM4P belonging to IFITM family can transcribe a functional long noncoding RNA termed lncRNA IFITM4P. Importantly, results showed that lncRNA IFITM4P was involved in innate antiviral immunity, which resembles some interferon-stimulated genes (ISGs). Furthermore, lncRNA IFITM4P was identified as a target of miR-24-3p and acts as a ceRNA to inhibit the replication of IAV through regulating the mRNA levels of IFITM1, IFITM2 and IFITM3. These data provide a new insight into the role of a previously uncharacterized lncRNA encoded by a pseudogene in the host antiviral response, and a better understanding of the IFITM antiviral network.

scholarly journals Opposing roles of endosomal innate immunity proteins IFITM3 and TLR7 in human metapneumovirus infection

2018 ◽  
Author(s):  
Temet M. McMichael ◽  
Yu Zhang ◽  
Adam D. Kenney ◽  
Lizhi Zhang ◽  
Mijia Lu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Plasma Membrane ◽  
Transmembrane Protein ◽  
Human Metapneumovirus ◽  
Toll Like Receptor ◽  
Entry Pathway ◽  
Hmpv Infection ◽  
Cellular Factors ◽  
Entry Strategy ◽  
Cellular Entry

ABSTRACTHuman metapneumovirus (hMPV) utilizes a bifurcated cellular entry strategy, fusing either with the plasma membrane or, after endocytosis, with the endosome membrane. Whether cellular factors restrict or enhance either entry pathway is largely unknown. We found that the interferon-induced transmembrane protein 3 (IFITM3) inhibits hMPV infection to an extent similar to endocytosis-inhibiting drugs, and an IFITM3 variant that accumulates at the plasma membrane in addition to its endosome localization provided increased virus restriction. Mechanistically, IFITM3 blocks hMPV F protein-mediated membrane fusion, and inhibition of infection was reversed by the membrane destabilizing drug amphotericin B. Conversely, we unexpectedly found that infection by some hMPV strains is enhanced by Toll-like receptor 7 (TLR7), an endosomal protein, suggesting that cellular entry via endocytosis may be particularly advantageous for hMPV despite eventual restriction of this pathway upon induction of IFITM3. Overall, our results identify IFITM3 and TLR7 as endosomal factors differentially regulating hMPV infection.

scholarly journals Supplementation with humic substances affects the innate immunity in layer hens in posfasting phase

2016 ◽  
pp. 5198-5210 ◽  
Author(s):  
Rosa Sanmiguel P ◽  
Iang Rondón B
Keyword(s):  
Innate Immunity ◽  
Humic Substances ◽  
Bactericidal Activity ◽  
Respiratory Burst ◽  
Phagocytic Index ◽  
The Third ◽  
Serum Bactericidal Activity ◽  
Layer Hens ◽  
Los Grupos ◽  
Bacterial Agglutination

ABSTRACT Objective. Asses the effect of supplementation with Humic substances (HS) over some innate immunity parameters (serum bactericidal activity, phagocytosis, bacterial agglutination, respiratory burst and lisozyme activity) in phase after fasting of layer hens. Materials and methods. 120 posfasting phase Hy Line Brown layer hens were taken which were distributed into four groups: The first and the second were supplemented with 0.1 and 0.2% of HS, respectively. The third group was supplemented with 0.25 mg/kg on levamisole hydrochloride and fourth group have no supplementation; during sixty days period. Blood samples were collected on 8th, 30th and 60th of experiment day. Results. The phagocytic index and respiratory burst increased significantly at day 30th in HS supplemented groups. Alike, serum bactericidal activity and lisozyme activity improved on 8 th day, nevertheless, changes were no evident latter. The bacterial agglutination was high in supplemented groups evaluated at everyone times. Conclusions. Results showed that HS behave as immunostimulant in the early phase after fasting layer hens. RESUMEN Objetivo. Evaluar el efecto de las sustancias húmicas (SH) sobre algunos parámetros de la inmunidad innata (actividad bactericida del suero, fagocitosis, aglutinación bacteriana, explosión respiratoria y actividad de la lisozima) en la fase posmuda de gallinas ponedoras. Materiales y métodos. Se utilizaron 120 gallinas ponedoras Hy Line Brown en la fase de posmuda, las cuales fueron divididas en cuatro grupos: Los dos primeros fueron suplementados con 0.1 y 0.2% de SH respectivamente, el tercer grupo fue suplementado con 0.25 mg/kg de Clorhidrato de levamisol y el cuarto grupo control sin suplemento; durante un período de 60 días. Las muestras sanguíneas se tomaron los días 8, 30 y 60 del experimento. Resultados. El Índice fagocítico y la explosión respiratoria se incrementaron significativamente a partir del día 30 de suplementación con SH. De la misma manera, la actividad bactericida del suero y la actividad de la lisozima aumentaron al día 8; no obstante no se evidenciaron cambios posteriores. La aglutinación bacteriana fue significativamente mayor en los grupos suplementados en todos los tiempos evaluados. Conclusiones. Los resultados demuestran que las SH se comportan como agentes inmunoestimulantes en la fase temprana de la posmuda en gallinas ponedoras Hy Line Brown.

scholarly journals The discovery of gene mutations making SARS-CoV-2 well adapted for humans: host-genome similarity analysis of 2594 genomes from China, the USA and Europe

2020 ◽  
Author(s):  
Weitao Sun
Keyword(s):  
Innate Immunity ◽  
Transmembrane Protein ◽  
Gene Mutations ◽  
Host Genome ◽  
Genomic Diversity ◽  
Reading Frame ◽  
Genes Encoding ◽  
The Usa ◽  
Novel Coronavirus

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense single-stranded virus approximately 30 kb in length, causes the ongoing novel coronavirus disease-2019 (COVID-19). Studies confirmed significant genome differences between SARS-CoV-2 and SARS-CoV, suggesting that the distinctions in pathogenicity might be related to genomic diversity. However, the relationship between genomic differences and SARS-CoV-2 fitness has not been fully explained, especially for open reading frame (ORF)-encoded accessory proteins. RNA viruses have a high mutation rate, but how SARS-CoV-2 mutations accelerate adaptation is not clear. This study shows that the host-genome similarity (HGS) of SARS-CoV-2 is significantly higher than that of SARS-CoV, especially in the ORF6 and ORF8 genes encoding proteins antagonizing innate immunity in vivo. A power law relationship was discovered between the HGS of ORF3b, ORF6, and N and the expression of interferon (IFN)-sensitive response element (ISRE)-containing promoters. This finding implies that high HGS of SARS-CoV-2 genome may further inhibit IFN I synthesis and cause delayed host innate immunity. An ORF1ab mutation, 10818G>T, which occurred in virus populations with high HGS but rarely in low-HGS populations, was identified in 2594 genomes with geolocations of China, the USA and Europe. The 10818G>T caused the amino acid mutation M37F in the transmembrane protein nsp6. The results suggest that the ORF6 and ORF8 genes and the mutation M37F may play important roles in causing COVID-19. The findings demonstrate that HGS analysis is a promising way to identify important genes and mutations in adaptive strains, which may help in searching potential targets for pharmaceutical agents.

scholarly journals Activity of Alzheimer’s γ-secretase is linked to changes of interferon-induced transmembrane proteins (IFITM) in innate immunity

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Annie Y. Yao ◽  
Riqiang Yan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immunity ◽  
Transmembrane Protein ◽  
Specific Interaction ◽  
Transmembrane Proteins ◽  
Amyloid Deposition ◽  
Amyloid Peptides ◽  
Secretase Activity ◽  
Ad Therapy

Abstract The activity of γ-secretase is critical to the pathogenesis of Alzheimer’s disease (AD). How its activity is regulated is intriguing and highly important for any AD therapy that focuses on reduction of toxic amyloid peptides and amyloid deposition in patients. Recently, interferon-induced transmembrane protein 3 (IFITM3) has been identified as a novel regulator of γ-secretase through a specific interaction. This commentary highlights this exciting study and provides an updated link of γ-secretase activity to innate immunity through IFITM3.

Neutrophil Respiratory Burst (Innate Immunity) During Ramadan

2007 ◽  
Vol 7 (6) ◽  
pp. 997-1000 ◽  
Author(s):  
A. Latifynia ◽  
M. Vojgani . ◽  
H. Jafarieh . ◽  
T. Abofazeli .
Keyword(s):  
Innate Immunity ◽  
Respiratory Burst ◽  
Neutrophil Respiratory Burst
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