GSE134315
ROCK1 translocates to the nucleus and inhibits human cytomegalovirus propagation
Rho-associated coiled-coil kinase (ROCK) protein is a central kinase that regulates numerous cellular functions, including cellular polarity, motility, proliferation and apoptosis. Here, we demonstrate that ROCK has antiviral properties and inhibition of its activity results in enhanced propagation of human cytomegalovirus (HCMV). We show that during HCMV infection ROCK1 translocates to the nucleus and concentrates in the nucleolus were it co-localizes with the stress related chaperone, heat shock cognate 71 kDa protein (Hsc70) . Gene expression measurements showed that inhibition of ROCK activity does not affect the cellular stress response. We further demonstrate that inhibition of myosin, one of the central targets of ROCK, also increases HCMV propagation, implying that the anti-viral activity of ROCK might be mediated by activation of the actomyosin network. Finally, we demonstrate that inhibition of ROCK results in increased levels of the tegument protein UL32 and of viral DNA in the cytoplasm, suggesting ROCK activity hinders the efficient egress of HCMV particles out of the nucleus. Altogether our findings illustrate ROCK activity restricts HCMV propagation and suggest this inhibitory effect may be mediated by suppression of capsid egress out of the nucleus. Overall design: samples of HCMV infected fibroblasts treated with ROCK inhibitor or with DMSO as control, in duplicates