Open AccessThe Interface between Methyltransferase and Polymerase of NS5 Is Essential for Flavivirus Replication
Author(s) -
Xiaodan Li,
Chao Shan,
Cheng Deng,
Han-Qing Ye,
Pei Yong Shi,
Zhiming Yuan,
Peng Gong,
Bo Zhang
Publication year - 2014
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0002891
Subject(s) - flavivirus , biology , polymerase , rna dependent rna polymerase , rna polymerase , genetics , methyltransferase , virology , viral replication , rna , virus , methylation , gene
The flavivirus NS5 harbors both a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP). Both enzyme activities of NS5 are critical for viral replication. Recently, the full-length NS5 crystal structure of Japanese encephalitis virus reveals a conserved MTase-RdRP interface that features two conserved components: a six-residue hydrophobic network and a GTR sequence. Here we showed for the first time that these key interface components are essential for flavivirus replication by various reverse genetics approaches. Interestingly, some replication-impaired variants generated a common compensatory NS5 mutation outside the interface (L322F), providing novel routes to further explore the crosstalk between MTase and RdRP.