Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35

Journal Article · Fri Mar 12 00:00:00 EST 2010 · Nat. Struct. Mol. Biol.

DOI:https://doi.org/10.1038/nsmb.1765· OSTI ID:1002274

Leung, Daisy W; Prins, Kathleen C; Borek, Dominika M; Farahbakhsh, Mina; Tufariello, JoAnn M; Ramanan, Parameshwaran; Nix, Jay C; Helgeson, Luke A; Otwinowski, Zbyszek; Honzatko, Richard B; Basler, Christopher F; Amarasinghe, Gaya K ^[1]

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1. Sinai

Ebola viral protein 35 (VP35), encoded by the highly pathogenic Ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I-like receptors. Here we report the crystal structure of the Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which together with in vivo results reveals how VP35-dsRNA interactions contribute to immune evasion. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are 'end-capped' by a pocket of hydrophobic residues that mimic RIG-I-like receptor recognition of blunt-end dsRNA. Residues critical for RNA binding are also important for interferon inhibition in vivo but not for viral polymerase cofactor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1002274
• Journal Information: Nat. Struct. Mol. Biol., Vol. 17, Issue (2) ; 02, 2010; ISSN 1545-9993
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
IN VIVO
INTERFERON
POLYMERASES
PROTEINS
RESIDUES
RNA