The RNA helicase DDX5, a new regulatory protein of Sindbis virus infection

RNA helicases emerge as key factors regulating host-virus interactions. In this study published in “Virology Journal”, scientists have demonstrated the role of the DDX5 helicase in the replication cycle of the Sindbis virus (SINV). They were able to show that this nuclear protein is capable of relocating to the cytoplasm during SINV virus infection and directly interacting with the viral capsid, conferring a pro-viral action.

RNA helicases are emerging as key regulators of viral infections. They are essential enzymes for the unfolding of RNA structures and play a crucial role in many cellular processes involving RNA, as well as in regulating various stages of viral cycles.

In this study, researchers investigated the impact of the human RNA helicase DDX5 on SINV infection, a model virus for studying other mosquito-transmitted emerging pathogens such as the Chikungunya virus. Using imaging and RNA immunoprecipitation approaches, they highlighted for the first time that DDX5 has the peculiarity of relocating from the nucleus to the cytoplasm of cells during infection by interacting with viral RNA. Furthermore, the analysis of DDX5 interactome by mass spectrometry in SINV-infected human cells identified new cellular and viral partners. The researchers identified a direct interaction between DDX5, its known cofactor DDX17, and the viral capsid. Scientists were able to demonstrate that the absence of DDX5 and its cofactor DDX17 in the cell reduces SINV infection. Conversely, overexpression of DDX5 has a positive impact on the virus, underscoring the central role played by DDX5 in host-virus interaction during the infectious cycle of SINV.

These results not only highlight that DDX5 is a novel host factor hijacked by SINV but also broaden our understanding of the roles played by DDX5 and DDX17 as regulators of viral infections. As the inhibition of both DDX5 and DDX17 reduces virus levels, further investigations are needed to better characterize these factors as potential targets for future antiviral therapies.

Messmer, M., Pierson, L., Pasquier, C. et al. DEAD box RNA helicase 5 is a new pro-viral host factor for Sindbis virus infection. Virol J. 21, 76 (2024).