Endoplasmic reticulum stress–activated unfolding response induced by SVCV infection in epithelioma papulosum cyprini (EPC) cells

Abstract Spring viremia of carp virus (SVCV) is an efficient pathogen that causes high mortality in the common carp. Endoplasmic reticulum stress (ERS) and activation of the unfolded protein response (UPR) play important roles in viral infection, replication, and in triggering host pathogenesis. However, the relationship between ERS and SVCV infection is unknown. Here, we reported that the SVCV is phosphorylated by cellular XBP1, in which specific splicing occurs and activates the IRE1-XBP1, PERK-eIF2α, and ATF6 signaling pathways. First, western blotting showed that the protein expression of GRP78 increased with the duration of infection, and eIF2ɑ protein expression also increased. Moreover, fluorescence-based quantitative PCR results showed that ERS marker GRP78 mRNA increased with time, and IRE1, XBP1, PERK, ATF4, and ATF6 mRNA levels also increased. Additionally, using tunicamycin (TM) as an ERS activator, the results showed that its optimal use concentration was 2.0 μg/mL, and the optimal use concentration of Tauroursodesoxycholic Acid (TUDCA) as an ERS inhibitor was 400 μM. In summary, SVCV virus replication could be promoted or inhibited using activation and inhibitors, and SVCV infection of EPC cells activated the IRE1-XBP1, PERK-eIF2ɑ, and ATF6 signaling pathways.