INVESTIGADORES
GAMARNIK Andrea Vanesa
artículos
Título:
A balance between circular and linear forms of the dengue virus genome is crucial for viral replication
Autor/es:
VILLORDO SM,; ALVAREZ DE,; GAMARNIK AV
Revista:
RNA (NEW YORK, N.Y.)
Editorial:
COLD SPRING HARBOR LAB PRESS
Referencias:
Lugar: NY; Año: 2010 vol. Dec. p. 2325 - 2335
ISSN:
1355-8382
Resumen:
The plasticity of viral plus strand RNA genomes is
fundamental for the multiple functions of these molecules. Local and long-range
RNA-RNA interactions provide the scaffold for interacting proteins of the
translation, replication, and encapsidation machinery. Using dengue virus as a
model, we investigated the relevance of the interplay between two alternative
conformations of the viral genome during replication. Flaviviruses require
long-range RNA-RNA interactions and genome cyclization for RNA synthesis. Here,
we define a sequence present in the viral 3UTR that overlaps two mutually
exclusive structures. This sequence can form an extended duplex by long range
5-3
interactions in the circular conformation of the RNA or fold locally into a
small hairpin (sHP) in the linear form of the genome. A mutational analysis of
the sHP structure revealed an absolute requirement of this element for viral
viability, suggesting the need of a linear conformation of the genome. Viral
RNA replication showed high vulnerability to changes that alter the balance
between circular and linear forms of the RNA. Mutations that shift the
equilibrium towards the circular or the linear conformation of the genome
spontaneously revert to sequences with different mutations that tend to restore
the relative stability of the two competing structures. We propose a model in
which the viral genome exists in at least two alternative conformations and the
balance between these two states is critical for infectivity.