The Interface between Methyltransferase and Polymerase of NS5 Is Essential for Flavivirus Replication

Xiao Dan Li; Chao Shan; Cheng Lin Deng; Han Qing Ye; Pei Yong Shi; Zhi Ming Yuan; Peng Gong; Bo Zhang

doi:10.1371/journal.pntd.0002891

The Interface between Methyltransferase and Polymerase of NS5 Is Essential for Flavivirus Replication

Xiao Dan Li, Chao Shan, Cheng Lin Deng, Han Qing Ye, Pei Yong Shi, Zhi Ming Yuan, Peng Gong, Bo Zhang

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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.

Original language	English (US)
Article number	e2891
Journal	PLoS neglected tropical diseases
Volume	8
Issue number	5
DOIs	https://doi.org/10.1371/journal.pntd.0002891
State	Published - May 2014
Externally published	Yes

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Infectious Diseases

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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.",

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AU - Gong, Peng

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AB - 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.

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The Interface between Methyltransferase and Polymerase of NS5 Is Essential for Flavivirus Replication

Abstract

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