Sub-genomic RNA of defective interfering (D.I.) dengue viral particles is replicated in the same manner as full length genomes

- Most dengue viruses in nature contain defective genomes and may act as D.I. particles.
- D.I. particles may be important for the effective transmission of infectious virions.
- The most extreme example of defective genomes have deletions of approximately 10,000 nucleotides.
- The retained 5′ and 3′ elements of DENV sub-genomic RNA are sufficient for their replication.
- The structure rather than the nucleotide sequence of these elements determines their function.

The predicted secondary structure of sub-genomic RNA in dengue virus defective interfering (D.I.) particles from patients, or generated in vitro, resembled that of the 3′ and 5′ regions of wild type dengue virus (DENV) genomes. While these structures in the sub-genomic RNA were found to be essential for its replication, their nucleotide sequences were not, so long as any new sequences maintained wild type RNA secondary structure. These observations suggested that these sub-genomic fragments of RNA from dengue viruses were replicated in the same manner as the full length genomes of their wild type, “helper”, viruses and that they probably represent the smallest fragments of DENV RNA that can be replicated during a natural infection. While D.I. particles containing sub-genomic RNA are completely parasitic, the relationship between wild type and D.I. DENV may be symbiotic, with the D.I. particles enhancing the transmission of infectious DENV.