Fig. 1

Structural organization and life cycle of DENV: A The Dengue virus genome comprises 5’UTR, ORF, and 3’UTR. The ORF translates into a polyprotein, which is further processed into three structural proteins: C (Capsid), E (Envelope), and M (Membrane), and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). B The initiation of the DENV replication cycle occurs with the entry into the cell via various host cell receptors or through the Fc region of the virus-antibody immune complex, which attaches to Fc receptors present on the target host cell. 1. DENV attaches to host cell receptors and enters the cell. 2. Internalization occurs through receptor-mediated endocytosis, forming an early endosome. 3, 4. Genome uncoating occurs as the pH decreases inside the early endosome; conformational changes take place, releasing the nucleocapsid into the cytoplasm. 5, 6. Disassembly of the nucleocapsid allows viral RNA assembly in the cytoplasm. 7. Viral RNA translocates into the Endoplasmic Reticulum, where translation results in a single polyprotein that is cleaved down by both host and viral proteases. Additionally, a translation switch results in the transcription of viral RNA employing antisense viral RNA. 8. The capsid protein encases the freshly created viral RNA to form the nucleocapsid. 9. Virus assembly occurs on the surface of the Endoplasmic Reticulum. 10. Immature viral particles are transported to the trans-Golgi network, where acidification results in conformational changes, followed by exposure to the furin protease to form mature viral particles. 11. Mature viral particles are exocytosed into the extracellular matrix, completing their replication cycle