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

- In the present manuscript we have shown that one of the Ebola virus proteins, VP24 can interfere with the activation of the RIG-I pathway.
- Here we show that EBOV VP24 inhibits the activation of the RIG-I pathway no matter at which level the RIG-I pathway is activated.
- VP24 works downstream of RIG-I, MAVS, TBK1/IKKe and IRF3 suggesting that VP24 functions in the nucleus inhibiting IFN gene expression.
- The mutated form of VP24 that does not bind STATs is not inhibiting IFN gene expression and the expression of IFN-induced genes like MxA.
- Our data thus provides a novel observation of innate immune inhibiting functions of EBOV VP24.

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.