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

Research output: Contribution to journalArticle

19 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 languageEnglish (US)
Pages (from-to)10717-10721
Number of pages5
JournalJournal of Virology
Volume89
Issue number20
DOIs
StatePublished - 2015
Externally publishedYes

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Reverse Genetics
Dengue virus
Dengue Virus
methyltransferases
Methyltransferases
Virus Replication
virus replication
Site-Directed Mutagenesis
Molecular Biology
Viruses
site-directed mutagenesis
viruses

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Medicine(all)

Cite this

Zhao, Y., Soh, T. S., Ki Chan, K. W., Yin Fung, S. S., Swaminathan, K., Lim, S. P., ... Vasudevan, S. G. (2015). Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication. Journal of Virology, 89(20), 10717-10721. https://doi.org/10.1128/JVI.01239-15

Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication. / Zhao, Yongqian; Soh, Tingjin Sherryl; Ki Chan, Kitti Wing; Yin Fung, Sarah Suet; Swaminathan, Kunchithapadam; Lim, Siew Pheng; Shi, Pei-Yong; Huber, Thomas; Lescar, Julien; Luo, Dahai; Vasudevan, Subhash G.

In: Journal of Virology, Vol. 89, No. 20, 2015, p. 10717-10721.

Research output: Contribution to journalArticle

Zhao, Y, Soh, TS, Ki Chan, KW, Yin Fung, SS, Swaminathan, K, Lim, SP, Shi, P-Y, Huber, T, Lescar, J, Luo, D & Vasudevan, SG 2015, 'Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication', Journal of Virology, vol. 89, no. 20, pp. 10717-10721. https://doi.org/10.1128/JVI.01239-15
Zhao, Yongqian ; Soh, Tingjin Sherryl ; Ki Chan, Kitti Wing ; Yin Fung, Sarah Suet ; Swaminathan, Kunchithapadam ; Lim, Siew Pheng ; Shi, Pei-Yong ; Huber, Thomas ; Lescar, Julien ; Luo, Dahai ; Vasudevan, Subhash G. / Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication. In: Journal of Virology. 2015 ; Vol. 89, No. 20. pp. 10717-10721.
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