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 prM protein of flaviviruses interacts with the E protein to form prM-E heterodimers, which are essential for the formation of immature virions. The prM protein is then cleaved to M protein through cellular proteases to produce and release mature virions. The M protein of flaviviruses contains two membrane-spanning domains and a short ectodomain. Histidine at residue 99 and the transmembrane region of the prM protein of JEV is critical for stable prM-E heterodimeric complex formation. 43 Moreover, a single amino acid substitution at the N-linked glycosylation site of the prM-E complex of JEV may elicit an enhanced host humoral immune response, which could be a useful strategy for vaccine design. 44 The functional roles of the V153M substitution, which is found in all the ZIKV epidemic strains, and other amino acid substitutions I125V, S139N, K143E, A148P, H157Y, V158I, K246R and V262A, which are different between the African and Asian lineages, may be of some importance in future studies.