Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35

Daisy W. Leung, Kathleen C. Prins, Dominika M. Borek, Mina Farahbakhsh, Joann M. Tufariello, Parameshwaran Ramanan, Jay C. Nix, Luke A. Helgeson, Zbyszek Otwinowski, Richard B. Honzatko, Christopher F. Basler, Gaya K. Amarasinghe

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalNature Structural and Molecular Biology
Volume17
Issue number2
DOIs
StatePublished - Feb 2010

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Double-Stranded RNA
Viral Proteins
Interferons
Immune Evasion
Ebolavirus
Antiviral Agents
RNA

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Leung, D. W., Prins, K. C., Borek, D. M., Farahbakhsh, M., Tufariello, J. M., Ramanan, P., ... Amarasinghe, G. K. (2010). Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35. Nature Structural and Molecular Biology, 17(2), 165-172. https://doi.org/10.1038/nsmb.1765

Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35. / 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.

In: Nature Structural and Molecular Biology, Vol. 17, No. 2, 02.2010, p. 165-172.

Research output: Contribution to journalArticle

Leung, DW, Prins, KC, Borek, DM, Farahbakhsh, M, Tufariello, JM, Ramanan, P, Nix, JC, Helgeson, LA, Otwinowski, Z, Honzatko, RB, Basler, CF & Amarasinghe, GK 2010, 'Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35', Nature Structural and Molecular Biology, vol. 17, no. 2, pp. 165-172. https://doi.org/10.1038/nsmb.1765
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. / Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35. In: Nature Structural and Molecular Biology. 2010 ; Vol. 17, No. 2. pp. 165-172.
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