Functions and Mechanisms of Flavivirus RNA Structures

LUANA DE BORBA; JUAN M. CARBALLEDA; SERGIO M. VILLORDO; ANDREA V. GAMARNIK; FRANCO L. MARSICO; HORACIO M. PALLARES

Congreso; XLI Annual Meeting of the Chilean Biochemistry and Molecular Biology Society; 2018

The Flavivirusgenus include a large number of emerging and re-emerging human pathogens that cycle between mosquitos andhumans including dengue, Zika and yellow fever.These viruses contain a single stranded RNA genome with a great deal ofinformation in RNA structures that function as signals to enhance, suppress orpromote viral replication. Natural sequence variability in these RNA structuresare determinants for viral epidemiological fitness, pathogenesis, hostadaptation and transmission between mosquitos and humans. An intriguing featureof the 3? untranslated region (UTR) of flavivirus genomes is the evolutionaryconservation of sequence repeats and duplicated RNA structures. In the case ofdengue, the 3?UTR contains two almost identical stem loop structures (SLI andSLII) and two similar dumbbell elements (DB1 and DB2).  We have previously defined that the SLsfacilitate host switching between mosquito and human cells. More recently, wefound that the DB elements play opposite functions during infection and areunder different selective pressures in the two hosts. Mechanistic analysisindicate that the DB elements modulate viral genome conformation and RNAreplication. Our results support a model in which a functional diversificationof duplicated RNA elements in the viral 3?UTR is driven by host specificrequirements. This study provides new ideas for understanding molecular aspectsof evolution of RNA viruses that jump between different species.