IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
RNA structure duplications in the dengue virus genome facilitates host adaptation.
Autor/es:
VILLORDO S *; FILOMATORI C * EQUAL CONTRIBUTION TO THIS WORK; GAMARNIK A
Lugar:
Belèm
Reunión:
Encuentro; Fourth Pan-American Dengue Network Meeting; 2014
Institución organizadora:
Pan American Dengue Research Network(Pan-Dengue Net)
Resumen:
Dengue virus cycles in nature between humans and mosquitoes, however, it
is still unclear how the virus adapts to use different cellular machineries for
replication and overcome different types of antiviral responses. RNA viruses in
general have high capacity to adapt to different environments due to the
genetic diversity of viral populations.
Using dengue virus, we recently found specific RNA sequences in the
viral 3'UTR that are essential for viral replication in mosquito cells but
dispensable for replication in mammalian cells. These studies provided direct
evidence for host-specific functions of viral RNA elements and raised the
question whether viral RNA structures are under specific selective pressures
during host adaptation. To further these studies, we evaluated how RNA
cis-acting elements evolve under single-host selective pressures in mosquito
and mammalian cells and during host switch.
Deep sequencing of dengue virus populations subjected to host adaptation
showed a strong selection of different mutations in the viral 3'UTR in each
host, while cis-acting elements present at the 5' end of the genome remained
unchanged. Secondary RNA structure analysis showed that viruses selected in
mosquito cells contained mutations mapping to a single stem-loop structure,
which was found to be duplicated in mosquito-borne flaviviruses. Using recombinant
viruses and evaluation of fitness parameters, we found that RNA duplication is
required to tolerate mosquito-adaptive mutations for replication in mammalian
cells. Our findings provide a novel model supporting the role of RNA
duplications for efficient dengue virus replication in multiple hosts.