Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic

Zhu, Zheng; Chan, Jasper Fuk-Woo; Tee, Kah-Meng; Choi, Garnet Kwan-Yue; Lau, Susanna Kar-Pui; Woo, Patrick Chiu-Yat; Tse, Herman; Yuen, Kwok-Yung

The major viral enzymes of flaviviruses are encoded by the NS3 and NS5 coding regions. In addition to its putative protease activity at the N terminus, the C-terminal domain of the NS3 protein of ZIKV also possesses putative ATPase/helicase, nucleoside triphosphatase, and 5ʹ-triphosphatase activities. The multiple roles of NS3 in the viral replication cycle make the protein an attractive antiviral target. NS5 is the largest and most conserved protein of ZIKV. The N-terminal part contains a putative methyltransferase domain with both N7 and 2ʹ-Omethyltransferase and guanyltransferase activities. The C-terminal part contains typical motifs of RdRp as in other flaviviruses. The NS5 protein of DENV mediates cleavage of STAT2, which is an important mediator in the host innate immune response signaling pathways. 59 In this study, we found that NS5, being the largest protein, also has the largest number of amino acid substitutions (n = 21) when the strains of African and Asian lineages are compared. Eight amino acid substitutions in the NS3 and NS5 are different between the preepidemic and epidemic strains, including M1970L, T2630V, A2783V, N2892S, K3046R, P3158S, S3219D and D3383N. The importance of these substitutions should be investigated further.