Fig. 3.

Schematic model of the dynamic exchange of proteins and viral RNA between replication compartments and the cytosol. Upon infection, the viral (+)RNA genome associates with the rough ER (ribosomes are indicated in dark grey) and the viral polyprotein, composed of structural (pink) and non-structural (green) proteins. Invaginations of the ER membrane are induced, leading to the formation of 80 nm vesicles that are connected with the cytosol by a pore [21]. Inside vesicles the viral RNA is replicated through a dsRNA intermediate. Newly generated (+)RNA is extruded from the vesicles into an extra-vesicular compartment where it is either translated, or further replicated or packaged (RNA “triage”). Packaging occurs on the ER membrane and new virus buds into the ER lumen. The extra-vesicular compartment is connected to the cytosol and accessible to proteins such as MS2-EYFP or TIA-1/TIAR, which bind the viral RNA to regulate viral translation and shuttle between the extra-vesicular compartment and stress granules (SG) [114]. Also RIG-I is freely diffusible into this compartment as shown in Fig. 2. This diagram is not drawn to scale.