Ebola virus VP35 has novel NTPase and helicase-like activities

Shu, Ting; Gan, Tianyu; Bai, Peng; Wang, Xiaotong; Qian, Qi; Zhou, Hui; Cheng, Qi; Qiu, Yang; Yin, Lei; Zhong, Jin; Zhou, Xi

VP35 has been reported to play pivotal roles in multiple processes of filoviral replication and pathogenesis. And it is intriguing to ask how the NTPase/helicase-like activity of VP35 functions in the life cycle of EBOV. VP35 is a cofactor of polymerase L and an essential component of filoviral RNP complex, which carries out the EBOV RNA replication and transcription. Thus, it is plausible that VP35 can work together with NP and L to mediate the unwinding of dsRNA intermediates produced during viral RNA replication/transcription, and/or can aid the rearrangement of the cis-acting elements within EBOV mRNA and genomic/antigenomic RNAs, thereby facilitating the transcription, translation and encapsidation of EBOV RNAs or allowing viral RNAs to switch among distinct processes. However, owing to technical limitations, virus-encoded RNA remodeling activities are usually studied in vitro, and it is mostly infeasible to measure the exact roles of RNA helicases on the structures and functionalities of viral RNAs in infected cells (56) . Indeed, GuHCl, an FDA-approved small compound and well-known inhibitor of certain viral helicases, including enterovirus 2C and norovirus NS3, is able to inhibit the NTPase/helicaselike activity of EBOV VP35 as well as EBOV minigenome replication/transcription in cells, implying the functional importance of the VP35-associated RNA remodeling activity in EBOV replication. Future advances in techniques may overcome the technical barriers and provide mechanistic and dynamic views of how VP35 remodels viral RNA molecules at different processes of EBOV life cycle.