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

25 Scopus citations

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 - Jan 1 2015

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Zhao, Y., Soh, T. S., Chan, K. W. K., Fung, S. S. Y., Swaminathan, K., Lim, S. P., Shi, P. Y., Huber, T., Lescar, J., Luo, D., & 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