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Comparative analysis reveals no consistent association between the secondary structure of the 3'-untranslated region of dengue viruses and disease syndrome

¹ Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Mueller Laboratory, University Park, PA 16802, USA
² Department of Virology, US Army Medical Component-Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
³ Military Infectious Diseases Research Program, US Army Medical Research and Materiel Command, Fort Detrick, MD 21702, USA
⁴ Queen Sirikit National Institute of Child Health, Bangkok, Thailand

Correspondence
Edward C. Holmes
ech15{at}psu.edu

A comparative analysis was performed of the 3'-untranslated region (UTR) of Dengue virus (DENV) sampled from Bangkok, Thailand, over a 30 year period and representing all four serotypes. Considerable genetic variation was observed both within and among serotypes. Notably, a full-length version of the critical 3'-long stable hairpin structure was absent from some isolates, suggesting the occurrence of complex structural interactions within the 3'-UTR, including the influence of upstream mutations. The Thai sequences were then combined with 61 globally sampled isolates of DENV taken from patients with either dengue fever or severe dengue disease. No consistent association was found between 3'-UTR secondary structure and the clinical outcome of DENV infection, although some evidence for a trend in this direction was observed in DENV-2. It was concluded that the 3'-UTR is not the sole determinant of DENV virulence in nature, although variation in secondary structure may greatly influence viral fitness.

Supplementary figures and tables are available in JGV Online.

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