Stromal Interaction Molecule 1 Promotes the Replication of vvIBDV by Mobilizing Ca in the ER.

Infectious bursal disease virus (IBDV) is one of the main threats to the poultry industry worldwide. Very virulent IBDV (vvIBDV) is a fatal virus strain that causes heavy mortality in young chicken flocks. Ca is one of the most universal and versatile signalling molecules and is involved in almost every aspect of cellular processes. Clinical examination showed that one of the characteristics of vvIBDV-infected chickens was severe metabolic disorders, and the chemical examination showed that their serum Ca level decreased significantly. However, there are limited studies on how vvIBDV infection modulates the cellular Ca level and the effect of Ca level changes on vvIBDV replication. In our study, we found Ca levels in the endoplasmic reticulum (ER) of vvIBDV-infected B cells were higher than that of mock-infected cells, and the expression level of stromal interaction molecule 1 (STIM1), an ER Ca sensor, was significantly upregulated due to vvIBDV infection. The knock-down expression of STIM1 led to decreased Ca level in the ER and suppressed vvIBDV replication, while the over-expressed STIM1 led to ER Ca upregulation and promoted vvIBDV replication. We also showed that the inhibition of Ca-release-activated-Ca (CRAC) channels could reduce vvIBDV infection by blocking Ca from entering the ER. This study suggests a new mechanism that STIM1 promotes the replication of vvIBDV by mobilizing Ca in the ER.