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Title: The Interface between Methyltransferase and Polymerase of NS5 Is Essential for Flavivirus Replication
Authors: Li X.-D.
Shan C.
Deng C.-L.
Ye H.-Q.
Shi P.-Y. 
Yuan Z.-M.
Gong P.
Zhang B.
Keywords: complementary DNA
nonstructural protein 5
RNA directed RNA polymerase
virus RNA
DNA directed RNA polymerase
NS5 protein, flavivirus
virus protein
animal cell
controlled study
enzyme activity
Flavivirus infection
gene mutation
gene sequence
genetic transfection
immunofluorescence microscopy
immunofluorescence test
Japanese encephalitis virus
luciferase assay
molecular interaction
reverse transcription polymerase chain reaction
RNA extraction
RNA replication
RNA transcription
virus genome
virus mutant
virus plaque
virus replication
amino acid sequence
cell line
chemical phenomena
molecular genetics
nucleotide sequence
sequence alignment
virus replication
Amino Acid Sequence
Cell Line
Conserved Sequence
DNA-Directed RNA Polymerases
Hydrophobic and Hydrophilic Interactions
Molecular Sequence Data
Sequence Alignment
Viral Nonstructural Proteins
Virus Replication
Issue Date: 2014
Citation: Li X.-D., Shan C., Deng C.-L., Ye H.-Q., Shi P.-Y., Yuan Z.-M., Gong P., Zhang B. (2014). The Interface between Methyltransferase and Polymerase of NS5 Is Essential for Flavivirus Replication. PLoS Neglected Tropical Diseases 8 (5) : e2891. ScholarBank@NUS Repository.
Abstract: 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. ? 2014 Li et al.
Source Title: PLoS Neglected Tropical Diseases
ISSN: 19352727
DOI: 10.1371/journal.pntd.0002891
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