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

Felix He; Krister Melén; Sari Maljanen; Rickard Lundberg; Miao Jiang; Pamela Österlund; Laura Kakkola; Ilkka Julkunen

doi:10.1016/j.virol.2017.06.002

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

Virology. 2017 Sep:509:23-34. doi: 10.1016/j.virol.2017.06.002. Epub 2017 Jun 5.

Authors

Felix He¹, Krister Melén², Sari Maljanen³, Rickard Lundberg⁴, Miao Jiang⁵, Pamela Österlund⁶, Laura Kakkola⁷, Ilkka Julkunen⁸

Affiliations

¹ Institute of Biomedicine/Virology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland. Electronic address: [email protected].
² Institute of Biomedicine/Virology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland; Expert Microbiology Unit, National Institute for Health and Welfare, Mannerheimintie 166, 00300 Helsinki, Finland. Electronic address: [email protected].
³ Institute of Biomedicine/Virology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland. Electronic address: [email protected].
⁴ Institute of Biomedicine/Virology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland. Electronic address: [email protected].
⁵ Expert Microbiology Unit, National Institute for Health and Welfare, Mannerheimintie 166, 00300 Helsinki, Finland. Electronic address: [email protected].
⁶ Expert Microbiology Unit, National Institute for Health and Welfare, Mannerheimintie 166, 00300 Helsinki, Finland. Electronic address: [email protected].
⁷ Institute of Biomedicine/Virology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland. Electronic address: [email protected].
⁸ Institute of Biomedicine/Virology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland. Electronic address: [email protected].

PMID: 28595092
DOI: 10.1016/j.virol.2017.06.002

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.

Keywords: Ebolavirus; Filovirus; Innate immunity; Interferon-λ1; RIG-I pathway; VP24.

MeSH terms

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

Substances

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