Substitution of NS5 N-terminal domain of dengue virus type 2 RNA with type 4 domain caused impaired replication and emergence of adaptive mutants with enhanced fitness

Tadahisa Teramoto, Siwaporn Boonyasuppayakorn, Misty Handley, Kyung H. Choi, Radhakrishnan Padmanabhan

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: The four dengue virus serotypes, evolved from a common ancestor, are global human pathogens. Results: Interserotypic substitution of the functional domain essential for 5′-capping was detrimental to RNA replication. Conclusion: The chimeric RNA gradually evolves replication fitness through adaptive mutations in genes encoding two replication proteins. Significance: This study provides a possible pathway for generating attenuated dengue virus vaccine.

Original languageEnglish (US)
Pages (from-to)22385-22400
Number of pages16
JournalJournal of Biological Chemistry
Volume289
Issue number32
DOIs
StatePublished - Aug 8 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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