INVESTIGADORES
ALVAREZ Diego Ezequiel
congresos y reuniones científicas
Título:
Role of RNA Regulatory Elements in Dengue Virus Replication
Autor/es:
ANDREA V. GAMARNIK; CLAUDIA V. FILOMATORI; MARIA F. LODEIRO; DIEGO E. ALVAREZ; NESTOR G. IGLESIAS
Lugar:
Recife
Reunión:
Congreso; First Pan-American Dengue Research Network Meeting; 2008
Institución organizadora:
Pan-American Dengue Research Network
Resumen:
The single plus stranded RNA genome of dengue and other flaviviruses is
amplified in the infected cell by a two-step process. First, the RNA
dependent RNA polymerase (RdRp), encoded in the viral protein NS5, makes
a complementary strand with negative polarity, which then, serves as a
template to copy multiple viral genomes. Molecular details of how the
viral RdRp recognizes and specifically amplifies flavivirus genomes
remain unclear. We have recently proposed a model for dengue virus RNA
amplification that involves a promoter element for polymerase activity
at the 5´ end of the genome and cyclization of the viral genome. Now, we
are studying how these cis-acting RNA elements participate in the
process. Using in vitro RNA polymerase assays and infectious viral RNAs,
the structural elements required for promoter activity and viral
replication were defined. These elements were found to be conserved
among different members of the Flavivirus genus, providing evidence for a
common mechanism of promoter mediated RNA synthesis. In addition,
mutations within the mapped element involved in genome cyclization
resulted in revertant viruses that reconstituted alternative secondary
and tertiary structures. These results suggest that fluctuating
conformation, between linear and circular forms of the genome, are
necessary for viral replication.