Your browser doesn't support javascript.
loading
FEAR antiviral response pathway is independent of interferons and countered by poxvirus proteins.
Rex, Emily A; Seo, Dahee; Chappidi, Sruthi; Pinkham, Chelsea; Brito Oliveira, Sabrynna; Embry, Aaron; Heisler, David; Liu, Yang; Munir, Moiz; Luger, Karolin; Alto, Neal M; da Fonseca, Flávio Guimarães; Orchard, Robert; Hancks, Dustin C; Gammon, Don B.
Afiliación
  • Rex EA; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Seo D; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Chappidi S; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Pinkham C; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Brito Oliveira S; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Embry A; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Heisler D; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Liu Y; Department of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
  • Munir M; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Luger K; Department of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
  • Alto NM; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • da Fonseca FG; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Orchard R; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Hancks DC; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Gammon DB; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Microbiol ; 9(4): 988-1006, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38538832
ABSTRACT
The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 binding to SUMOylated hSpt16 and by tethering SUMOylated hSpt16 to microtubules. Furthermore, A51R antagonism of FACT enhances poxvirus replication in human cells and virulence in mice. Finally, we show that FACT also restricts rhabdoviruses, flaviviruses and orthomyxoviruses, suggesting broad roles for FACT in antiviral immunity. Our study reveals the FACT-ETS-1 antiviral response (FEAR) pathway to be critical for eukaryotic antiviral immunity and describes a unique mechanism of viral immune evasion.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferones / Evasión Inmune Límite: Animals / Humans Idioma: En Revista: Nat Microbiol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferones / Evasión Inmune Límite: Animals / Humans Idioma: En Revista: Nat Microbiol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido