Dengue Virus Genome Translation and Replication

The genetic material of the Dengue virus (DENV) is a positive sense single-strand RNA molecule (+ssRNA) that, upon release into the host cell cytosol, can directly be translated by host cell ribosomes (reviewed in Rodenhuis-Zybert et al. 2010). The translation of the DENV genomic RNA produces a single polyprotein that is co- and post-translationally cleaved by both viral and host proteases into three structural proteins (C, prM, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) (reviewed in Rodenhuis-Zybert et al. 2010). The polyprotein's signal- and stop-transfer sequences direct its back-and-forth translocation across the endoplasmic reticulum (ER) membrane (reviewed in Rodenhuis-Zybert et al. 2010).

The DENV replication complex assembles at and is anchored to the endoplasmic reticulum (ER) membrane, where it forms specialized structures called replication vesicles or replication organelles (reviewed in Paul & Bartenschlager, 2015).

The replication of the DENV genomic RNA involves the synthesis of the negative sense RNA (-ssRNA) intermediate, in which the DENV replication complex uses the genomic +ssRNA as a template to synthesize a complementary -ssRNA molecule. Subsequently, this -ssRNA serves as a template for the production of new +ssRNA genomes. Newly synthesized genomic +ssRNA molecules can be used for further translation, to produce more viral proteins, or can be packaged into new virions.

The DENV genomic +ssRNA is 5′-capped with a unique 5′-stem-loop structure (SLA for stem-loop A), which is essential for RNA replication and 5′ capping. The fate of viral RNA during translation, replication and assembly is reviewed in Hodge et al., 2019 and Abram et al., 2024.