The genus Flavivirus including Japanese encephalitis virus, Dengue virus, and Zika virus all of which are mosquito-borne human pathogen and cause serious diseases in humans. BCL2 family proteins control mitochondria-mediated apoptosis to maintain cell homeostasis via the removal of damaged cells and pathogen-infected cells. In this study, we examined the roles of BCL2 proteins in the induction of apoptosis in cells infected with flaviviruses. We found that survival of the infected cells depends on BCLX_L, a pro-survival BCL2 protein due to suppression of the expression of another pro-survival protein, MCL1. Haploinsufficiency of the BCLX_L gene, as well as administration of BCLX_L inhibitors, increased survival rate after challenge of JEV infection. These results suggest that BCLX_L plays a crucial role in the survival of cells infected with flaviviruses, and that BCLX_L may provide a novel antiviral target to suppress propagation of the family of Flaviviridae viruses.

This article was published in Plos Pathogens on Sept 9.

Infection with flaviviruses requires BCLX_L for cell survival

Suzuki T, Okamoto T, Katoh H, Sugiyama Y, Kusakabe S, Tokunaga M, Hirano J, Miyata Y, Fukuhara T, Ikawa M, Satoh T, Yoshio S, Suzuki R, Saijo M, Huang DCS, Kanto T, Akira S, Matsuura Y.