Published in

American Society for Microbiology, Journal of Virology, 20(89), p. 10717-10721, 2015

DOI: 10.1128/jvi.01239-15

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Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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.