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

An interesting question raised by the current study is that: if RNA remodelling activities are so important to viruses, why helicase or helicase-like activity has never been found in NNSVs before? Indeed, numerous, if not all, DNA viruses and positive-sense RNA viruses have been found to encode their own helicases, which share the conserved NTPase/helicase signature motifs with various host helicases of diverse organisms ranging from prokaryotes to eukaryotes (62, 63) . Based on the conserved motifs, putative helicases can be predicted by bioinformatic algorithms before being biochemically confirmed and characterized. And the lack of conserved helicase signature motifs within EBOV VP35 should be the reason why the NTPase/helicase-like activities were not predicted and identified previously. Moreover, the high conservation of helicase signature motifs suggests that various viral and host helicases share similar origins. On the other hand, the NTPase/helicase-like activities of EBOV VP35 should be evolved independently, suggesting that filoviruses (and probably other NNSVs) have an earlier evolutionary divergence with positive-sense RNA viruses before the latter 'acquire' canonical helicases. More importantly, in the absence of a canonical helicase, EBOV manages to obtain a helicaselike activity instead, highlighting its functional necessity to EBOV. Given that all the members of Filoviridae encode VP35 proteins, which are functionally analogous to the P proteins of other NNSVs (5), future studies by us and others should investigate whether the NTPase/helicase activities are general to other filoviral VP35 as well as NNSV P proteins.