Figure 1.

The life cycle of RV. (1) The infectious RV TLPs adhere to the specific receptors present in lipid rafts of the host cellular plasma membrane. (2) Following receptor-mediated endocytosis and trafficking along the endosomal pathway, (3) RV TLPs shed their outermost layer and release DLPs into the cytoplasm. (4) Within DLPs, viral RNAs are transcribed with VP1 acting as a polymerase to yield (+)ssRNAs that are eventually capped by another viral protein VP3. (5) Subsequently, structural and nonstructural proteins are synthesized from RV (+)ssRNAs on cellular ribosomes. (6) NSP5 and NSP2 essentially lead to the nucleation of viroplasms on host cellular lipid droplet (LD) scaffold. (7) Inside the maturing viroplasms, accumulating VP1, VP2 and VP3 participate in the viral genome replication. Within the VP2-encaged viral cores, VP2-driven polymerase activity of VP1 initiates the biogenesis of (-)ssRNAs. De novo synthesized cores acquire the VP6 layer to form the progeny DLPs. (8) The DLPs enter into the morphogenetic assembly pathway by acquiring an outer capsid which occurs by a budding step through the ER-derived cellular membrane where VP6 on DLPs docks on NSP4 on ER-derived membrane. Inside the ER, progeny particles acquire a transient envelope. (9) Subsequently, the transient envelope dissipates, NSP4 is stripped off, and the outermost VP7-VP4 layer is assembled. Alternatively, acquisition of VP4 spikes may occur on VP7-surrounded virions within the ER-Golgi intermediate compartment (ERGIC)/plasma membrane lipid raft domains (10a) before non-lytic virion release. (10b) RV progenies may also exit through lytic mechanisms. Of note, the time kinetics of RV life cycle events is dependent on many factors most important of which are the RV strains and the host cell lines used for infection as well as the multiplicity of infection. In general, in the RV permissive cell line MA104 infected with a simian RV strain SA11 at a multiplicity of infection 3, the timeline of infection is as follows: 0-4 hours post infection (hpi) includes the early life cycle events such as the viral adsorption, entry, endosomal trafficking, initiation of transcription and translation and viroplasm nucleation; 4-8 hpi includes viroplasm maturation and concurrent viral replication, secondary transcription, and initiation of the morphogenetic assembly pathway within maturing viroplasms; 8-12 hpi includes the late life cycle events such as the morphogenetic maturation and viral release.