INVESTIGADORES
ALVAREZ Diego Ezequiel
artículos
Título:
Functional analysis of dengue virus cyclization sequences located at the 5' and 3'UTRs
Autor/es:
DIEGO E. ALVAREZ; CLAUDIA V. FILOMATORI; ANDREA V. GAMARNIK
Revista:
VIROLOGY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 2008 vol. 375 p. 223 - 235
ISSN:
0042-6822
Resumen:
Flavivirus RNA replication involves cyclization of the viral genome. A
model for this process includes a promoter element at the 5' end of the
genome and long-range RNA-RNA interactions. Two pairs of complementary
sequences present at the ends of the viral RNA, known as 5'-3'CS and
5'-3'UAR, have been proposed to be involved in dengue virus genome
cyclization. The requirement of 5'-3'CS complementarity for viral
replication has been experimentally demonstrated for dengue and other
mosquito borne flaviviruses. Here, we performed a functional analysis to
study the role of 5'-3'UAR sequences using genomic and subgenomic
dengue virus RNAs. We found that single mutations disrupting 5'-3'
complementarity greatly compromised viral RNA synthesis. Although in
most of the cases incorporation of compensatory mutations re-established
viral RNA replication, certain nucleotides were found to be involved in
alternative secondary structures also important for viral replication.
In addition, mutations within 5' or 3'UAR in the context of an
infectious dengue virus RNA resulted in spontaneous mutations that
restored UAR base pairings. Together, we propose that specific UAR
nucleotides as well as 5'-3'UAR complementarity constitute cis-acting
signals involved in amplification of the dengue virus genome.