Fig 7. A model on the roles of p33-mediated recruitment of Rab5-positive endosomes in the formation of large tombusviral replication compartments.

At the early stage of tombusvirus replication, TBSV-induced spherule formation may take place in the existing peroxisomal membranes. At the peak time of replication, occurring at a late stage at which point the viral components are much more abundant due to ongoing translation of viral RNAs, however, a portion of p33 molecules co-opt the PE-rich Rab5-positive endosomes via p33–GTP-Rab5 interaction using the actin cables. These processes lead to the formation of large replication compartments containing aggregated peroxisomes fused with PE-rich Rab5-positive endosomes, providing the suitable microenvironment for building numerous spherules harboring the active tombusvirus VRCs. We envision similar early and peak/late stages with CIRV, except the involvement of mitochondria in building the viral replication compartment.