Cellular Importin-α3 Expression Dynamics in the Lung Regulate Antiviral Response Pathways against Influenza A Virus Infection.
Cell Rep
; 31(3): 107549, 2020 04 21.
Article
in En
| MEDLINE
| ID: mdl-32320654
ABSTRACT
Importin-α adaptor proteins orchestrate dynamic nuclear transport processes involved in cellular homeostasis. Here, we show that importin-α3, one of the main NF-κB transporters, is the most abundantly expressed classical nuclear transport factor in the mammalian respiratory tract. Importin-α3 promoter activity is regulated by TNF-α-induced NF-κB in a concentration-dependent manner. High-level TNF-α-inducing highly pathogenic avian influenza A viruses (HPAIVs) isolated from fatal human cases harboring human-type polymerase signatures (PB2 627K, 701N) significantly downregulate importin-α3 mRNA expression in primary lung cells. Importin-α3 depletion is restored upon back-mutating the HPAIV polymerase into an avian-type signature (PB2 627E, 701D) that can no longer induce high TNF-α levels. Importin-α3-deficient mice show reduced NF-κB-activated antiviral gene expression and increased influenza lethality. Thus, importin-α3 plays a key role in antiviral immunity against influenza. Lifting the bottleneck in importin-α3 availability in the lung might provide a new strategy to combat respiratory virus infections.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Influenza A virus
/
Orthomyxoviridae Infections
/
Alpha Karyopherins
/
Influenza, Human
Limits:
Animals
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Cell Rep
Year:
2020
Document type:
Article
Affiliation country:
Alemania