Genome circularization and RNA virus replication

Approximately 50 million people are infected with dengue virus each year, resulting in about 24,000 deaths world-wide. Dengue virus is a mosquito-borne member of the flavivirus family, whose other members cause encephalitis, hemorrhagic fevers, and hepatitis.

Dengue virus is a plus strand RNA virus that replicates its genome by a viral-encoded RNA-dependent RNA polymerase. Dr. Gamarnik and colleagues identified a structure at the 5' end of the RNA genome – what they term the “SLA” – that is recognized by the viral RNA polymerase. The replication machinery is then able, through the circularization of the dengue virus genome, to interact with the 3' initiation site, thousands of nucleotides downstream, and to initiate replication of the dengue virus genome.

The authors hypothesis that “Since similar 5'-3' long-range interactions were observed in many viral RNA genomes, the mechanism proposed for DV may represent a wide-spread strategy for viral RNA replication.”