Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza.
Med Microbiol Immunol
; 208(6): 869-876, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31172279
ABSTRACT
Influenza infection is common worldwide with many individuals affected each year during epidemics and occasionally pandemics. Previous studies in animal models and a few human cases have established an important role of innate type I and III interferon (IFN) for viral elimination and mounting of antiviral responses. However, genetic and immunological determinants of very severe disseminated influenza virus infection in humans remain incompletely understood. Here, we describe an adult patient with severe influenza virus A (IAV) infection, in whom we identified a rare variant E331V in IFN regulatory factor (IRF)7 by whole-exome sequencing. Examination of patient cells demonstrated a cellular phenotype suggesting functional IRF7 impairment, since priming with IFN was almost abolished and IFN responses to IAV were significantly impaired in patient cells. Moreover, IAV replication was significantly higher in patient cells than in controls. Finally, expression of IRF7 E331V in HEK293 cells demonstrated significantly reduced activation of both IFNA7 and IFNB promoters in a luciferase reporter gene expression assay compared to IRF7 wild type. These findings provide further support for the essential role of IRF7 in amplifying antiviral IFN responses to ensure potent and sustained IFN responses during influenza virus infection in humans.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
Interferones
/
Mutación Missense
/
Factor 7 Regulador del Interferón
/
Gripe Humana
/
Inmunidad Innata
/
Factores Inmunológicos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Med Microbiol Immunol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Dinamarca