Ebolavirus protein VP24 interferes with innate immune responses by inhibiting interferon-λ1 gene expression.

Abstract

Ebolaviruses (EBOV) cause severe disease with a recent outbreak in West Africa in 2014-2015 leading to more than 28 000 cases and 11 300 fatalities. This emphasizes the urgent need for better knowledge on these highly pathogenic RNA viruses. Host innate immune responses play a key role in restricting the spread of a viral disease. In this study we systematically analyzed the effects of cloned EBOV genes on the main host immune response to RNA viruses: the activation of RIG-I pathway and type I and III interferon (IFN) gene expression. EBOV VP24, in addition of inhibiting IFN-induced antiviral responses, was found to efficiently inhibit type III IFN-λ1 gene expression. This inhibition was found to occur downstream of IRF3 activation and to be dependent on VP24 importin binding residues. These results emphasize the importance of VP24 in EBOV infection cycle, making VP24 as an excellent target for drug development.

• Authors: Felix He, Krister Melén, Sari Maljanen, Rickard Lundberg, Miao Jiang, Pamela Österlund, Laura Kakkola, Ilkka Julkunen
• Journal: Virology (Virology) Vol. 509 Pg. 23-34 (Sep 2017) ISSN: 1096-0341 [Electronic] United States
• PMID: 28595092 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• interferon-lambda, human
• Interleukins
• VP24 protein, Ebola virus
• Viral Proteins
• Interferons

Topics

• Cell Line
• Ebolavirus (immunology, pathogenicity)
• Gene Expression Regulation
• Host-Pathogen Interactions
• Humans
• Immune Evasion
• Immunity, Innate
• Interferons
• Interleukins (antagonists & inhibitors)
• Viral Proteins (metabolism)