Inhibitor of sarco/endoplasmic reticulum calcium-ATPase impairs paramyxovirus replication

Abstract

21Sarco/endoplasmic reticulum calcium-ATPase (SERCA) is a membrane bound 22 cytosolic enzyme that is known to regulate the uptake of calcium into the 23 sarco/endoplasmic reticulum. Herein, we demonstrate for the first time that SERCA can 24 also regulate paramyxovirus [Peste des petits ruminants virus (PPRV) and Newcastle 25 disease virus (NDV)] replication. Treatment of Vero cells with SERCA specific 26 inhibitor (Thapsigargin) at a concentration that is nontoxic to the cells significantly 27 reduced virus replication. Conversely, overexpression of SERCA rescued the inhibitory 28 effect of Thapsigargin on virus replication. PPRV/NDV infection induced SERCA 29 expression in Vero cells which could be blocked by Thapsigargin. With the help of 30 time-of-addition and virus step-specific assays, it was observed that Thapsigargin 31 specifically inhibits viral entry and subcellular localization of the viral proteins. 32