Structural and Functional Studies of the Promoter Element for Dengue Virus RNA Replication

  • Lodeiro M
  • Filomatori C
  • Gamarnik A
130Citations
Citations of this article
211Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The 5′ untranslated region (5′UTR) of the dengue virus (DENV) genome contains two defined elements essential for viral replication. At the 5′ end, a large stem-loop (SLA) structure functions as the promoter for viral polymerase activity. Next to the SLA, there is a short stem-loop that contains a cyclization sequence known as the 5′ upstream AUG region (5′UAR). Here, we analyzed the secondary structure of the SLA in solution and the structural requirements of this element for viral replication. Using infectious DENV clones, viral replicons, and in vitro polymerase assays, we defined two helical regions, a side stem-loop, a top loop, and a U bulge within SLA as crucial elements for viral replication. The determinants for SLA-polymerase recognition were found to be common in different DENV serotypes. In addition, structural elements within the SLA required for DENV RNA replication were also conserved among different mosquito- and tick-borne flavivirus genomes, suggesting possible common strategies for polymerase-promoter recognition in flaviviruses. Furthermore, a conserved oligo(U) track present downstream of the SLA was found to modulate RNA synthesis in transfected cells. In vitro polymerase assays indicated that a sequence of at least 10 residues following the SLA, upstream of the 5′UAR, was necessary for efficient RNA synthesis using the viral 3′UTR as template.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Lodeiro, M. F., Filomatori, C. V., & Gamarnik, A. V. (2009). Structural and Functional Studies of the Promoter Element for Dengue Virus RNA Replication. Journal of Virology, 83(2), 993–1008. https://doi.org/10.1128/jvi.01647-08

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 94

64%

Researcher 42

28%

Lecturer / Post doc 7

5%

Professor / Associate Prof. 5

3%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 66

45%

Biochemistry, Genetics and Molecular Bi... 50

34%

Medicine and Dentistry 16

11%

Immunology and Microbiology 16

11%

Save time finding and organizing research with Mendeley

Sign up for free