Rotavirus infection induces G1 to S phase transition in MA104 cells via Ca⁺²/Calmodulin pathway.

ABSTRACT

Viruses, obligate cellular parasites rely on host cellular functions and target the host cell cycle for their own benefit. In this study, effect of rotavirus infection on cell cycle machinery was explored. We found that rotavirus (RV) infection in MA104 cells induces the expression of cyclins and cyclin dependent kinases and down-regulates expression of CDK inhibitors, resulting in G1 to S phase transition. The rotavirus induced S phase accumulation was found to be concurrent with induction in expression of calmodulin and activation of CaMKI which is reported as inducer of G1-S phase transition. This cell cycle manipulation was found to be Ca(+2)/Calmodulin pathway dependent. The physiological relevance of G1 to S phase transition was established when viral gene expressions as well as viral titers were found to be increased in S phase synchronized cells and decreased in G0/G1 phase synchronized cells compared to unsynchronized cells during rotavirus infection.