Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication

Yongqian Zhao; Tingjin Sherryl Soh; Kitti Wing ki Chan; Sarah Suet Yin Fung; Kunchithapadam Swaminathan; Siew Pheng Lim; Pei Yong Shi; Thomas Huber; Julien Lescar; Dahai Luo; Subhash G. Vasudevan

doi:10.1128/JVI.01239-15

Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication

Yongqian Zhao, Tingjin Sherryl Soh, Kitti Wing ki Chan, Sarah Suet Yin Fung, Kunchithapadam Swaminathan, Siew Pheng Lim, Pei Yong Shi, Thomas Huber, Julien Lescar, Dahai Luo^*, Subhash G. Vasudevan

^*Corresponding author for this work

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

40 Citations (Scopus)

Abstract

We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.

Original language	English
Pages (from-to)	10717-10721
Number of pages	5
Journal	Journal of Virology
Volume	89
Issue number	20
DOIs	https://doi.org/10.1128/JVI.01239-15
Publication status	Published - 1 Jan 2015

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title = "Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication",

abstract = "We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.",

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AU - Zhao, Yongqian

AU - Soh, Tingjin Sherryl

AU - Chan, Kitti Wing ki

AU - Fung, Sarah Suet Yin

AU - Swaminathan, Kunchithapadam

AU - Lim, Siew Pheng

AU - Shi, Pei Yong

AU - Huber, Thomas

AU - Lescar, Julien

AU - Luo, Dahai

AU - Vasudevan, Subhash G.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.

AB - We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.

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DO - 10.1128/JVI.01239-15

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SP - 10717

EP - 10721

JO - Journal of Virology

JF - Journal of Virology

IS - 20

ER -

Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication

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