Nana Yan,Yongqiang Wang,Zehua Chen,Aijing Liu,Yue Li,Bo Yang,Kai Li,Xiaole Qi,Yulong Gao,Li Gao,Changjun Liu,Yanping Zhang,Hongyu Cui,Qing Pan,Xiaomei Wang

Viruses.2022 Jul 13;14(7):1524.doi: 10.3390/v14071524.

Abstract

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. Ca₂₊ 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 Ca₂₊ level decreased significantly. However, there are limited studies on how vvIBDV infection modulates the cellular Ca₂₊ level and the effect of Ca₂₊ level changes on vvIBDV replication. In our study, we found Ca₂₊ 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 Ca₂₊ sensor, was significantly upregulated due to vvIBDV infection. The knock-down expression of STIM1 led to decreased Ca₂₊ level in the ER and suppressed vvIBDV replication, while the over-expressed STIM1 led to ER Ca₂₊ upregulation and promoted vvIBDV replication. We also showed that the inhibition of Ca₂₊-release-activated-Ca₂₊ (CRAC) channels could reduce vvIBDV infection by blocking Ca₂₊ from entering the ER. This study suggests a new mechanism that STIM1 promotes the replication of vvIBDV by mobilizing Ca₂₊ in the ER.

Keywords: Ca2+; STIM1; vvIBDV.