Triple IFN pathway deficiency sensitizes mice to human respiratory virus infection independent of human viral receptor expression.

ingentiumby ingentium

In Coronavirus Literature.

Publication date: Jul 16, 2026

Interferon (IFN) pathways form the innate barrier against viral invasion and partial deficiency in these pathways allows human virus infection. Whether a complete IFN pathway deficiency could confer the susceptibility to human viral infection independent of expressing the human viral receptor remains unknown. We develop an innate immunity severely deficient mouse model, designated AGL, which features one-step knock-out of the IFNAR, IFNGR and IFNLR. The AGL mice become susceptible to diverse representative human respiratory viruses, including adenovirus type 55 (HAdV-55; double-stranded DNA), human monkeypox virus (MPXV) clade IIb (double-stranded DNA), parainfluenza virus (PIV; negative-sense single-stranded RNA), and the clinically isolated SARS-CoV-2 delta variant (positive-sense single-stranded RNA). Our results suggest that the type III IFN pathway constitutes a backup layer of antiviral frontline beneath the type I and II IFN pathways. In addition, proof-of-concept studies testing MPXV and PIV antivirals highlight the translational value of AGL mice. The AGL mice, as a universal model, substantially enhance the ability to investigate both emerging and established viruses without the need for tailored mouse models.

Open Access PDF

Concepts Keywords
Agl
Deficiency
Ifn
Independent
Infection
Innate
Model
Pathway
Pathways
Receptor
Respiratory
Stranded
Viral
Virus
Viruses

Semantics

Type Source Name
disease MESH virus infection
disease MESH monkeypox
disease MESH parainfluenza
drug DRUGBANK (S)-Des-Me-Ampa
drug DRUGBANK Guanosine
pathway REACTOME Reproduction
disease MESH included
disease MESH Infectious Diseases
pathway REACTOME Metabolism
drug DRUGBANK Coenzyme M
disease MESH avian influenza
disease MESH severe acute respiratory syndrome
disease MESH Middle East respiratory syndrome
disease MESH influenza
disease MESH respiratory infections
disease MESH infection
disease MESH hepatitis
pathway KEGG Viral replication
pathway REACTOME Immune System
drug DRUGBANK Methyl isocyanate
disease MESH SARS CoV 2 infection
disease MESH dengue
disease MESH strains
disease MESH herpes simplex
pathway KEGG Virion
disease MESH adenovirus infection
disease MESH pneumonia
disease MESH weight loss
disease MESH interstitial pneumonia
disease MESH edema
disease MESH injury
drug DRUGBANK Cycloserine
disease MESH DCs
disease MESH fibrosis
disease MESH inflammation
disease MESH rash
disease MESH Emergency
disease MESH bronchopneumonia
drug DRUGBANK Cidofovir
disease MESH body weight
pathway REACTOME Interferon Signaling
disease MESH death
disease MESH AT1
disease MESH lung injury
pathway REACTOME Apoptosis
pathway KEGG Oxidative phosphorylation
disease MESH asymptomatic infection
drug DRUGBANK Angiotensin II
drug DRUGBANK L-Tyrosine
disease MESH pregnancy complications
disease MESH fed
disease MESH APC
disease MESH co infection
disease MESH body weight changes
drug DRUGBANK Water
drug DRUGBANK Phosphate ion
disease MESH PBS
drug DRUGBANK Sodium lauryl sulfate
disease MESH SDS
drug DRUGBANK Aspartame
drug DRUGBANK Tromethamine
disease MESH Rad
drug DRUGBANK Trypsin
disease MESH FBS
drug DRUGBANK Streptomycin
disease MESH hemorrhage
disease MESH necrosis
drug DRUGBANK Human Serum Albumin
disease MESH vaccinia
drug DRUGBANK Ethanol
pathway REACTOME Digestion
pathway REACTOME Signal amplification
drug DRUGBANK Medical air
disease MESH Image
disease MESH STAR
drug DRUGBANK Tamsulosin
pathway REACTOME Release
disease MESH Dis
disease MESH Respiratory syncytial virus infection
disease MESH Norovirus infection
disease MESH diarrhea
disease MESH Acute Lung Injury
disease MESH Ebola hemorrhagic fever
pathway REACTOME Infectious disease
disease MESH West Nile virus infection
disease MESH Keratitis
disease MESH anosmia
disease MESH Plan

Original Article

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Triple IFN pathway deficiency sensitizes mice to human respiratory virus infection independent of human viral receptor expression.

ingentiumby ingentium

In Coronavirus Literature.

Publication date: Jul 16, 2026

Interferon (IFN) pathways form the innate barrier against viral invasion and partial deficiency in these pathways allows human virus infection. Whether a complete IFN pathway deficiency could confer the susceptibility to human viral infection independent of expressing the human viral receptor remains unknown. We develop an innate immunity severely deficient mouse model, designated AGL, which features one-step knock-out of the IFNAR, IFNGR and IFNLR. The AGL mice become susceptible to diverse representative human respiratory viruses, including adenovirus type 55 (HAdV-55; double-stranded DNA), human monkeypox virus (MPXV) clade IIb (double-stranded DNA), parainfluenza virus (PIV; negative-sense single-stranded RNA), and the clinically isolated SARS-CoV-2 delta variant (positive-sense single-stranded RNA). Our results suggest that the type III IFN pathway constitutes a backup layer of antiviral frontline beneath the type I and II IFN pathways. In addition, proof-of-concept studies testing MPXV and PIV antivirals highlight the translational value of AGL mice. The AGL mice, as a universal model, substantially enhance the ability to investigate both emerging and established viruses without the need for tailored mouse models.

Open Access PDF

Concepts Keywords
Agl
Deficiency
Ifn
Independent
Infection
Innate
Model
Pathway
Pathways
Receptor
Respiratory
Stranded
Viral
Virus
Viruses

Semantics

Type Source Name
disease MESH virus infection
disease MESH monkeypox
disease MESH parainfluenza
drug DRUGBANK (S)-Des-Me-Ampa
drug DRUGBANK Guanosine
pathway REACTOME Reproduction
disease MESH included
disease MESH Infectious Diseases
pathway REACTOME Metabolism
drug DRUGBANK Coenzyme M
disease MESH avian influenza
disease MESH severe acute respiratory syndrome
disease MESH Middle East respiratory syndrome
disease MESH influenza
disease MESH respiratory infections
disease MESH infection
disease MESH hepatitis
pathway KEGG Viral replication
pathway REACTOME Immune System
drug DRUGBANK Methyl isocyanate
disease MESH SARS CoV 2 infection
disease MESH dengue
disease MESH strains
disease MESH herpes simplex
pathway KEGG Virion
disease MESH adenovirus infection
disease MESH pneumonia
disease MESH weight loss
disease MESH interstitial pneumonia
disease MESH edema
disease MESH injury
drug DRUGBANK Cycloserine
disease MESH DCs
disease MESH fibrosis
disease MESH inflammation
disease MESH rash
disease MESH Emergency
disease MESH bronchopneumonia
drug DRUGBANK Cidofovir
disease MESH body weight
pathway REACTOME Interferon Signaling
disease MESH death
disease MESH AT1
disease MESH lung injury
pathway REACTOME Apoptosis
pathway KEGG Oxidative phosphorylation
disease MESH asymptomatic infection
drug DRUGBANK Angiotensin II
drug DRUGBANK L-Tyrosine
disease MESH pregnancy complications
disease MESH fed
disease MESH APC
disease MESH co infection
disease MESH body weight changes
drug DRUGBANK Water
drug DRUGBANK Phosphate ion
disease MESH PBS
drug DRUGBANK Sodium lauryl sulfate
disease MESH SDS
drug DRUGBANK Aspartame
drug DRUGBANK Tromethamine
disease MESH Rad
drug DRUGBANK Trypsin
disease MESH FBS
drug DRUGBANK Streptomycin
disease MESH hemorrhage
disease MESH necrosis
drug DRUGBANK Human Serum Albumin
disease MESH vaccinia
drug DRUGBANK Ethanol
pathway REACTOME Digestion
pathway REACTOME Signal amplification
drug DRUGBANK Medical air
disease MESH Image
disease MESH STAR
drug DRUGBANK Tamsulosin
pathway REACTOME Release
disease MESH Dis
disease MESH Respiratory syncytial virus infection
disease MESH Norovirus infection
disease MESH diarrhea
disease MESH Acute Lung Injury
disease MESH Ebola hemorrhagic fever
pathway REACTOME Infectious disease
disease MESH West Nile virus infection
disease MESH Keratitis
disease MESH anosmia
disease MESH Plan

Original Article

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Your email address will not be published. Required fields are marked *

Triple IFN pathway deficiency sensitizes mice to human respiratory virus infection independent of human viral receptor expression.

ingentiumby ingentium

In Coronavirus Literature.

Publication date: Jul 16, 2026

Interferon (IFN) pathways form the innate barrier against viral invasion and partial deficiency in these pathways allows human virus infection. Whether a complete IFN pathway deficiency could confer the susceptibility to human viral infection independent of expressing the human viral receptor remains unknown. We develop an innate immunity severely deficient mouse model, designated AGL, which features one-step knock-out of the IFNAR, IFNGR and IFNLR. The AGL mice become susceptible to diverse representative human respiratory viruses, including adenovirus type 55 (HAdV-55; double-stranded DNA), human monkeypox virus (MPXV) clade IIb (double-stranded DNA), parainfluenza virus (PIV; negative-sense single-stranded RNA), and the clinically isolated SARS-CoV-2 delta variant (positive-sense single-stranded RNA). Our results suggest that the type III IFN pathway constitutes a backup layer of antiviral frontline beneath the type I and II IFN pathways. In addition, proof-of-concept studies testing MPXV and PIV antivirals highlight the translational value of AGL mice. The AGL mice, as a universal model, substantially enhance the ability to investigate both emerging and established viruses without the need for tailored mouse models.

Open Access PDF

Concepts Keywords
Agl
Deficiency
Ifn
Independent
Infection
Innate
Model
Pathway
Pathways
Receptor
Respiratory
Stranded
Viral
Virus
Viruses

Semantics

Type Source Name
disease MESH virus infection
disease MESH monkeypox
disease MESH parainfluenza
drug DRUGBANK (S)-Des-Me-Ampa
drug DRUGBANK Guanosine
pathway REACTOME Reproduction
disease MESH included
disease MESH Infectious Diseases
pathway REACTOME Metabolism
drug DRUGBANK Coenzyme M
disease MESH avian influenza
disease MESH severe acute respiratory syndrome
disease MESH Middle East respiratory syndrome
disease MESH influenza
disease MESH respiratory infections
disease MESH infection
disease MESH hepatitis
pathway KEGG Viral replication
pathway REACTOME Immune System
drug DRUGBANK Methyl isocyanate
disease MESH SARS CoV 2 infection
disease MESH dengue
disease MESH strains
disease MESH herpes simplex
pathway KEGG Virion
disease MESH adenovirus infection
disease MESH pneumonia
disease MESH weight loss
disease MESH interstitial pneumonia
disease MESH edema
disease MESH injury
drug DRUGBANK Cycloserine
disease MESH DCs
disease MESH fibrosis
disease MESH inflammation
disease MESH rash
disease MESH Emergency
disease MESH bronchopneumonia
drug DRUGBANK Cidofovir
disease MESH body weight
pathway REACTOME Interferon Signaling
disease MESH death
disease MESH AT1
disease MESH lung injury
pathway REACTOME Apoptosis
pathway KEGG Oxidative phosphorylation
disease MESH asymptomatic infection
drug DRUGBANK Angiotensin II
drug DRUGBANK L-Tyrosine
disease MESH pregnancy complications
disease MESH fed
disease MESH APC
disease MESH co infection
disease MESH body weight changes
drug DRUGBANK Water
drug DRUGBANK Phosphate ion
disease MESH PBS
drug DRUGBANK Sodium lauryl sulfate
disease MESH SDS
drug DRUGBANK Aspartame
drug DRUGBANK Tromethamine
disease MESH Rad
drug DRUGBANK Trypsin
disease MESH FBS
drug DRUGBANK Streptomycin
disease MESH hemorrhage
disease MESH necrosis
drug DRUGBANK Human Serum Albumin
disease MESH vaccinia
drug DRUGBANK Ethanol
pathway REACTOME Digestion
pathway REACTOME Signal amplification
drug DRUGBANK Medical air
disease MESH Image
disease MESH STAR
drug DRUGBANK Tamsulosin
pathway REACTOME Release
disease MESH Dis
disease MESH Respiratory syncytial virus infection
disease MESH Norovirus infection
disease MESH diarrhea
disease MESH Acute Lung Injury
disease MESH Ebola hemorrhagic fever
pathway REACTOME Infectious disease
disease MESH West Nile virus infection
disease MESH Keratitis
disease MESH anosmia
disease MESH Plan

Original Article

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Your email address will not be published. Required fields are marked *