Viral targeting of TFIIB impairs de novo polymerase II recruitment and affects antiviral immunity.
PLoS Pathog
; 14(4): e1006980, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29709033
ABSTRACT
Viruses have evolved a plethora of mechanisms to target host antiviral responses. Here, we propose a yet uncharacterized mechanism of immune regulation by the orthomyxovirus Thogoto virus (THOV) ML protein through engaging general transcription factor TFIIB. ML generates a TFIIB depleted nuclear environment by re-localizing it into the cytoplasm. Although a broad effect on gene expression would be anticipated, ML expression, delivery of an ML-derived functional domain or experimental depletion of TFIIB only leads to altered expression of a limited number of genes. Our data indicate that TFIIB is critically important for the de novo recruitment of Pol II to promoter start sites and that TFIIB may not be required for regulated gene expression from paused promoters. Since many immune genes require de novo recruitment of Pol II, targeting of TFIIB by THOV represents a neat mechanism to affect immune responses while keeping other cellular transcriptional activities intact. Thus, interference with TFIIB activity may be a favourable site for therapeutic intervention to control undesirable inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Transcrição Gênica
/
Proteínas Virais
/
Regulação da Expressão Gênica
/
Thogotovirus
/
Fator de Transcrição TFIIB
/
Influenza Humana
Limite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha