Deciphering the mechanisms of the FHL1 interactions with chikungunya virus. – CHIKHOST

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for crippling disease in humans. At present, there is no commercially available antiviral agents or vaccines to treat CHIKV infection. We have just identified the FHL1 protein as a major host factor for CHIKV replication. FHL1 is highly expressed by CHIKV target cells and is important for CHIKV permissiveness and pathogenesis. FHL1 interacts with the viral protein nsP3 to promote CHIKV genome amplification. We hypothesize that engagement of FHL1 by CHIKV will explain how infection, tissue targeting, and disease pathogenesis occurs. The primary goals of CHIKHOST are to define the precise mechanism(s) by which FHL1 mediates CHIKV replication, to gain structural insight into FHL1/nsP3 interaction, and to determine the detailed role of FHL1 in the pathogenesis of CHIKV in vivo using animal models. This proposal should bring insights into CHIKV disease and will facilitate the development of anti-CHIKV therapy.