title: DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function.
abstract: The Zaire Ebola virus (EBOV) protein VP35 is multifunctional; it inhibits IFN-α/β production and functions as a cofactor of the viral RNA polymerase. Mass spectrometry identified the double stranded RNA binding protein 76 (DRBP76/NFAR-1/NF90) as a cellular factor that associates with the VP35 C-terminal interferon inhibitory domain (IID). DRBP76 is described to regulate host cell protein synthesis and play an important role in host defense. The VP35-IID-DRBP76 interaction required the addition of exogenous dsRNA, but full-length VP35 associated with DRBP76 in the absence of exogenous dsRNA. Cells infected with a Newcastle disease virus (NDV)-expressing VP35 redistributed DRBP76 from the nucleus to the cytoplasm, the compartment in which EBOV replicates. Overexpression of DRBP76 did not alter the ability of VP35 to inhibit type I IFN production but did impair the function of the EBOV transcription/replication complex. These data suggest that DRBP76, via its association with VP35, exerts an anti-EBOV function.
authors: Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Reed S
authors: RS
authors: Shabman
authors: Daisy W
authors: DW
authors: Leung
authors: Joshua
authors: J
authors: Johnson
authors: Nicole
authors: N
authors: Glennon
authors: Erol E
authors: EE
authors: Gulcicek
authors: Kathryn L
authors: KL
authors: Stone
authors: Lawrence
authors: L
authors: Leung
authors: Lisa
authors: L
authors: Hensley
authors: Gaya K
authors: GK
authors: Amarasinghe
authors: Christopher F
authors: CF
authors: Basler
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism*; D029043:Ebolavirus / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D009522:Newcastle disease virus / Q000235:genetics; D050779:Nuclear Factor 90 Proteins / Q000235:genetics / Q000378:metabolism*; D011070:Poly I-C; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded; D014709:Vero Cells; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C429643:ILF3 protein, human; D050779:Nuclear Factor 90 Proteins; D012330:RNA, Double-Stranded; C080980:VP35 protein, filovirus; D054334:Viral Regulatory and Accessory Proteins; D016899:Interferon-beta; D012321:DNA-Directed RNA Polymerases; D011070:Poly I-C