Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication
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Zhao, Yongqian
Soh, Tingjin Sherryl
Chan, Kitti Wing Ki
Fung, Sarah Suet Yin
Swaminathan, Kunchithapadam
Lim, Siew Pheng
Shi, Pei-Yong
Lescar, Julien
Luo, Dahai
Vasudevan, Subhash
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American Society for Microbiology
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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Journal of Virology
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Open Access
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