Calcium-sensing receptor acts as an antiviral factor for rotavirus infections and participates in cellular antiviral response

Objective(s): Rotavirus (RV) is one of the most significant pathogens associated with childhood diarrhoeal deaths worldwide. Elevated cytoplasmic calcium is required for RV replication, but the underlying mechanisms responsible for calcium influx remain poorly understood. The Calcium-sensing receptor (CaSR) is an important Ca۲+ sensor that regulates the transport of Ca۲+ into or out of the extracellular space by affecting the status of Ca۲+ ion channels on the membrane of cells. Currently, the function of CaSR in RV replication is unclear. Materials and Methods: We evaluated the mRNA and protein levels of CaSR in RV-infected cells using qRT-PCR and Western blotting, respectively. Furthermore, we silenced or overexpressed CaSR in Caco-۲ cells using siRNA or a CaSR gene contained adenovirus (Adv-CaSR). qRT-PCR, plaque assay, and Western blotting were used to determine the synthesis of virus genomic RNA, production of progeny virion, and the levels of viral proteins. The content of Ca۲+ in cells was observed under confocal microscopy. Results: Compared with control cells, the RV-infected cells presented significantly decreased CaSR expression. Moreover, adenoviral-mediated over-expression or induction of CaSR by R۵۶۸ greatly inhibited the RV RNA synthesis, protein expression, and formation of viroplasm plaques, thereby suppressing RV replication. In contrast, CaSR-silenced cells exhibited significantly enhanced RV replication. Compared with the Adv-Control group, the concentration of cytosolic Ca۲+ significantly decreased in the Adv-CaSR group. Conclusion: These findings demonstrated that CaSR is a potential target for inhibition of RV replication. Therefore, enhancing the expression of CaSR might protect hosts from RV infections.

Keywords:

Calcium-sensing receptor , Diarrhea , Infection , Replication , Rotavirus