Fig. 9.

Schematic model of alphavirus propagation in the absence of capsid. Once the alphavirus RNA genome without capsid (alphavirus-ΔC) is delivered to the cytoplasm of a cell, it will replicate leading to the production of many genomic (gRNA) and subgenomic (sgRNA) copies. The envelope glycoproteins E1 and p62 will be translated from sgRNAs at the endoplasmic reticulum (ER) where they will form heterodimers that will be transported to the plasma membrane through Golgi. In late Golgi, p62 will mature to E2 by furin cleavage, rendering the spikes functional for fusion. iMVs will form when gRNAs get trapped inside pleomorphic microvesicles which are generated by budding at the plasma membrane. These iMVs, which have functional spikes on their surface, can interact with alphavirus receptors on neighbouring cells and enter them through endocytosis. The low pH of endosomes will trigger conformational changes on the spike glycoproteins, leading to the fusion of the iMV membrane and the endosome, resulting in the release of gRNA to the cytoplasm