Fueling Type I Interferonopathies: Regulation and Function of Type I Interferon Antiviral Responses

2019 ◽  
Vol 39 (7) ◽  
pp. 383-392 ◽  
Author(s):  
Chen Seng Ng ◽  
Hiroki Kato ◽  
Takashi Fujita
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Antiviral Responses ◽  
And Function ◽  
Type I Interferonopathies

Cloning and expression of membrane anchored glycoprotein G major lineal determinants implicated in triggering host cell antiviral responses mediated by type I interferon

2013 ◽  
Vol 34 (6) ◽  
pp. 1665
Author(s):  
A. Martínez-López ◽  
V. Chico ◽  
P. García-Valtanen ◽  
M. Ortega-Villaizan ◽  
S. Imad-Cheikh ◽  
...  
Keyword(s):  
Host Cell ◽  
Type I Interferon ◽  
Cloning And Expression ◽  
Type I ◽  
Antiviral Responses ◽  
Glycoprotein G

Nasopharyngeal metatranscriptome profiles of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study

2021 ◽  
pp. 2102293
Author(s):  
Yoshihiko Raita ◽  
Marcos Pérez-Losada ◽  
Robert J. Freishtat ◽  
Andrea Hahn ◽  
Eduardo Castro-Nallar ◽  
...  
Keyword(s):  
Clustering Analysis ◽  
Type I Interferon ◽  
Species Level ◽  
Type I ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
B Virus ◽  
End Products ◽  
And Function ◽  
Multicentre Prospective Study

The question addressed by the studyBronchiolitis is not only the leading cause of hospitalisation in U.S. infants but also a major risk factor for asthma development. Growing evidence supports clinical heterogeneity within bronchiolitis. To identify metatranscriptome profiles of infant bronchiolitis, and examine their relationship with host transcriptome and subsequent asthma development.Materials/patients and methodsAs part of multicentre prospective cohort study of infants (age <12 months) hospitalised for bronchiolitis, we integrated virus and nasopharyngeal metatranscriptome (species-level taxonomy and function) data measured at hospitalisation. We applied network-based clustering approaches to identify metatranscriptome profiles. We then examined their association with host transcriptome at hospitalisation and risk for developing asthma.ResultsWe identified five metatranscriptome profiles of bronchiolitis (n=244):A) virusRSVmicrobiomecommensals, B) virusRSV/RV-AmicrobiomeH.influenzae,C) virusRSVmicrobiomeS.pneumoniae, D) virusRSVmicrobiomeM.nonliquefaciens, andE) virusRSV/RV-CmicrobiomeM.catarrhalis. Compared with profile A, profile B infants were characterised by high proportion of eczema, H. influenzae abundance, and enriched virulence related to antibiotic resistance. These profile B infants also had upregulated TH17 and downregulated type I interferon pathways (FDR<0.005) and significantly higher risk for developing asthma (17.9% versus 38.9%; adjOR, 2.81; 95%CI, 1.11–7.26). Likewise, profile C infants were characterised by high proportion of parental asthma, S. pneumoniae dominance, and enriched glycerolipid and glycerophospholipid metabolism of microbiome. These profile C infants had upregulated receptor for advanced glycation end products signalling pathway (FDR<0.005) and higher risk of asthma (17.9% versus 35.6%; adjOR, 2.49; 95%CI, 1.10–5.87).Answer to the questionMetatranscriptome and clustering analysis identified biologically-distinct metatranscriptome profiles that have differential risks of asthma.

scholarly journals Type I Interferon Protects Mice from Fatal Neurotropic Infection with Langat Virus by Systemic and Local Antiviral Responses

2014 ◽  
Vol 88 (21) ◽  
pp. 12202-12212 ◽  
Author(s):  
E. Weber ◽  
K. Finsterbusch ◽  
R. Lindquist ◽  
S. Nair ◽  
S. Lienenklaus ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Antiviral Responses ◽  
Langat Virus

scholarly journals Type I interferon–mediated monogenic autoinflammation: The type I interferonopathies, a conceptual overview

2016 ◽  
Vol 213 (12) ◽  
pp. 2527-2538 ◽  
Author(s):  
Mathieu P. Rodero ◽  
Yanick J. Crow
Keyword(s):  
Lupus Erythematosus ◽  
Clinical Medicine ◽  
Type I Interferon ◽  
Treatment Options ◽  
Clinical Importance ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I ◽  
Monogenic Diseases ◽  
Type I Interferonopathies

Type I interferon is a potent substance. As such, the induction, transmission, and resolution of the type I interferon–mediated immune response are tightly regulated. As defined, the type I interferonopathies represent discrete examples of a disturbance of the homeostatic control of this system caused by Mendelian mutations. Considering the complexity of the interferon response, the identification of further monogenic diseases belonging to this disease grouping seems likely, with the recognition of type I interferonopathies becoming of increasing clinical importance as treatment options are developed based on an understanding of disease pathology and innate immune signaling. Definition of the type I interferonopathies indicates that autoinflammation can be both interferon and noninterferon related, and that a primary disturbance of the innate immune system can “spill over” into autoimmunity in some cases. Indeed, that several non-Mendelian disorders, most particularly systemic lupus erythematosus and dermatomyositis, are also characterized by an up-regulation of type I interferon signaling suggests the possibility that insights derived from this work will have relevance to a broader field of clinical medicine.

scholarly journals Pepscan Mapping of Viral Hemorrhagic Septicemia Virus Glycoprotein G Major Lineal Determinants Implicated in Triggering Host Cell Antiviral Responses Mediated by Type I Interferon

2010 ◽  
Vol 84 (14) ◽  
pp. 7140-7150 ◽  
Author(s):  
V. Chico ◽  
A. Martinez-Lopez ◽  
M. Ortega-Villaizan ◽  
A. Falco ◽  
L. Perez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Antigen ◽  
Type I Interferon ◽  
Viral Hemorrhagic Septicemia Virus ◽  
Type I ◽  
Type I Ifn ◽  
Viral Glycoprotein ◽  
Antiviral Responses ◽  
Viral Hemorrhagic Septicemia ◽  
Glycoprotein G

ABSTRACT Surface glycoproteins of enveloped virus are potent elicitors of type I interferon (IFN)-mediated antiviral responses in a way that may be independent of the well-studied genome-mediated route. However, the viral glycoprotein determinants responsible for initiating the IFN response remain unidentified. In this study, we have used a collection of 60 synthetic 20-mer overlapping peptides (pepscan) spanning the full length of glycoprotein G (gpG) of viral hemorrhagic septicemia virus (VHSV) to investigate what regions of this protein are implicated in triggering the type I IFN-associated immune responses. Briefly, two regions with ability to increase severalfold the basal expression level of the IFN-stimulated mx gene and to restrict the spread of virus among responder cells were mapped to amino acid residues 280 to 310 and 340 to 370 of the gpG protein of VHSV. In addition, the results obtained suggest that an interaction between VHSV gpG and integrins might trigger the host IFN-mediated antiviral response after VHSV infection. Since it is known that type I IFN plays an important role in determining/modulating the protective-antigen-specific immune responses, the identification of viral glycoprotein determinants directly implicated in the type I IFN induction might be of special interest for designing new adjuvants and/or more-efficient and cost-effective viral vaccines as well as for improving our knowledge on how to stimulate the innate immune system.

scholarly journals Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses

2018 ◽  
Vol 4 (5) ◽  
pp. eaar2824 ◽  
Author(s):  
Qingxiang Liu ◽  
Yaoxing Wu ◽  
Yunfei Qin ◽  
Jiajia Hu ◽  
Weihong Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Type I Interferon ◽  
Family Members ◽  
Type I ◽  
Interferon Signaling ◽  
Antiviral Responses

scholarly journals Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy

2019 ◽  
Author(s):  
Conor Gruber ◽  
Marta Martin-Fernandez ◽  
Fatima Ailal ◽  
Xueer Qiu ◽  
Justin Taft ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Transcriptional Activity ◽  
Type I Interferon ◽  
Early Response ◽  
Type I ◽  
Homozygous State ◽  
Gain Of Function ◽  
Monogenic Disorders ◽  
Sterically Hinder ◽  
Type I Interferonopathies

AbstractType I interferonopathies are monogenic disorders characterized by enhanced Type I interferon (IFN-I) activity. Inherited ISG15 and USP18 deficiencies underlie type I interferonopathies by preventing the regulation of late responses to IFN-I. Specifically, ISG15/USP18 are induced by IFN-I and sterically hinder JAK1 from binding to the IFNAR2 subunit of IFN-I receptor. We report an infant who died of autoinflammation due to a homozygous missense mutation (R148Q) in STAT2. The variant is gain-of-function (GOF) for ISGF3-dependent induction of late but not early response to IFN-I. Surprisingly, the mutation does not enhance the intrinsic transcriptional activity of ISGF3. Rather, the STAT2 R148Q variant is GOF because it fails to appropriately interact with and traffic USP18 to IFNAR2, preventing USP18 from negatively regulating responses to IFN-I. Overall, a STAT2 missense mutation that fails to facilitate USP18-mediated signal termination in the homozygous state underlies a novel genetic etiology of type I interferonopathy.

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