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© Institut Pasteur
Culture de myotubes murins infectés par le virus de la rage fixe, observée en immunoflorescence indirecte.
Publication : Cell reports

Marburgvirus hijacks nrf2-dependent pathway by targeting nrf2-negative regulator keap1

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell reports - 13 Mar 2014

Page A, Volchkova VA, Reid SP, Mateo M, Bagnaud-Baule A, Nemirov K, Shurtleff AC, Lawrence P, Reynard O, Ottmann M, Lotteau V, Biswal SS, Thimmulappa RK, Bavari S, Volchkov VE

Link to Pubmed [PMID] – 24630992

Cell Rep 2014 Mar;6(6):1026-36

Marburg virus (MARV) has a high fatality rate in humans, causing hemorrhagic fever characterized by massive viral replication and dysregulated inflammation. Here, we demonstrate that VP24 of MARV binds Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of nuclear transcription factor erythroid-derived 2 (Nrf2). Binding of VP24 to Keap1 Kelch domain releases Nrf2 from Keap1-mediated inhibition promoting persistent activation of a panoply of cytoprotective genes implicated in cellular responses to oxidative stress and regulation of inflammatory responses. Increased expression of Nrf2-dependent genes was demonstrated both during MARV infection and upon ectopic expression of MARV VP24. We also show that Nrf2-deficient mice can control MARV infection when compared to lethal infection in wild-type animals, indicating that Nrf2 is critical for MARV infection. We conclude that VP24-driven activation of the Nrf2-dependent pathway is likely to contribute to dysregulation of host antiviral inflammatory responses and that it ensures survival of MARV-infected cells despite these responses.

http://www.ncbi.nlm.nih.gov/pubmed/24630992