Figure 3.

Host cellular contribution in regulating viroplasm condensation and maturation. RV blocks mitotic entry of the host cell cycle by prolonging intra S-phase retention. This is enabled by the depletion of cyclin B1 and subsequent inhibition of the Cdk1-cyclin B1 complex by multiple RV proteins. Inhibition of mitotic entry ensures the preservation of hyperacetylated and stabilized microtubular structures which along with the kinesin motor protein Eg5 and dynein facilitate viroplasmic condensation and peri-nuclear relocalization. Targeting microtubule, Eg5 kinesin, and dynein intermediate chain by small molecules nocodazole, monastrol, and dynapyrazole-A respectively, impairs viroplasm dynamics. RV also activates MRN-ATM-Chk2 branch of DDR during infection in absence of nuclear DNA damage and λ-H2AX positive nuclear foci. Moreover, MRN components, ATM and Chk2 relocate to the cytoplasm and co-localize with viroplasms. Targeting Mre11, ATM, and Chk2 by small molecule inhibitors Mirin, KU55933, and BML-277, respectively, antagonize RV replication. KU55933 and BML-277 prevent viroplasm condensation and maturation.