Fig 6.

IRE1α promotes SARS-CoV-2 viral RNA replication independently of viral entry. (A) Hek293 + ACE2 cells were pre-treated with small molecule IRE1α inhibitors or DMSO solvent control prior to infection with SARS-CoV-2 spike pseudotyped lentivirus or mock infection. Reporter virus infection was assessed 72 hours later by measuring luciferase activity, which is shown on a log scale. (B–D) Calu-3 cells were treated with IRE1α nuclease inhibitor 4μ8C or DMSO solvent control prior to infection with ΔS-SARS-CoV-2 single-cycle virus replicon particles. RNA was harvested 24 hours post-infection, and the relative abundance of spliced XBP1 (B), ERDJ4 (C), or SARS-CoV-2 E gene (D) was determined by quantitative RT-PCR. Data are means ± SD of eight (A) or five (B) replicates and are representative of two (A) or three (B–D) independent experiments, respectively. *P < 0.05 by unpaired t-test. ND, not detected.