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

Besides filoviruses, non-segmented, negative-sense RNA viruses (NNSVs) in the order Mononegavirales include numerous important human and zoonotic pathogens, such as rabies virus, Nipah virus, respiratory syncytial virus, human parainfluenza viruses, measles virus, mumps virus, etc. (5, 6) . NNSVs share common organizations of viral genomic RNAs and similar strategies of transcription and replication (5) . For filoviruses, the (-)-sense viral genomic RNA is approximately 19 kb in length and encodes seven open reading frames (ORFs) for all the viral proteins, i.e. nucleoprotein (NP), viral protein 35 (VP35), VP40, glycoprotein (GP), VP30, VP24, and the large polymerase protein (L) (7) (8) (9) . Upon viral entry into host cells, the released viral genomic (-)-RNAs are used as the templates for the transcription of individual viral mRNAs that are translated into filoviral proteins. The viral genomic (-)-RNAs are then switched to replicate the antigenomic positive-sense (+)-RNAs, which are used as the templates for the production of progeny viral genomic (-)-RNAs (7) . The transcription and replication of EBOV RNAs are carried out by the viral ribonucleoprotein (RNP) complex that contains the RNAdependent RNA polymerase (RdRP) L, the polymerase cofactor VP35 (10, 11) , as well as NP and VP30 (12) , which represent the minimal elements required for EBOV transcription and replication (13) .