Cellular receptors and host factors mediating orthoflavivirus entry

Figures

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  Fig. 1. Structural organization of orthoflaviviruses and host factors involved in initial viral attachment. (A) Schematic representation of an orthoflavivirus particle, showing the lipid envelope, envelope-associated proteins, capsid, and positive-sense RNA genome. (B) Surface arrangement and structural organization of the flaviviral envelope (E) protein, which mediates receptor engagement and pH-dependent membrane fusion. (C) Early attachment of orthoflaviviruses to host cells through glycosaminoglycans, C-type lectin receptors such as DC-SIGN and the mannose receptor, and antibody-dependent enhancement mediated by Fcγ receptors. These molecules promote viral concentration at the cell surface and may facilitate subsequent receptor-mediated endocytosis, although not all function as bona fide internalization receptors

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  Fig. 2. Entry and intracellular life cycle of orthoflaviviruses. Orthoflaviviruses first attach to host-cell surface molecules and entry-associated factors, including PHB1/2, NCAM1, TIM1, integrins, and LDLR-family proteins, depending on virus species and cell type. Following receptor-mediated endocytosis, acidification of endosomal compartments triggers E protein rearrangement, membrane fusion, and release of the positive-sense RNA genome into the cytoplasm. viral RNA is translated into a single polyprotein at the endoplasmic reticulum, which is subsequently processed by host and viral proteases. Viral replication occurs in ER-derived replication organelles, followed by capsid recruitment, virion assembly in ER cisternae, maturation through the secretory pathway, and extracellular release. Autophagy-associated secretory routes may contribute to viral egress in selected flavivirus–host systems