HEV blocks the MPTP opening, and genetic silencing of the MPTP regulator enhances viral replication. A–E) Flow cytometry analysis of MPTP opening in Huh7.5 cells (A–D) and in Huh7.5-p6 infectious cells (E) by measuring retained fluorescence after treatment with the indicated molecules for 15 min. F) Mean retained fluorescence ± sem, from 4 independent experiments. **P < 0.01 vs. PBS control. G) Western-blot analysis of CypD expression in Huh7.5- and U87-based p6 infectious cells transduced with lentiviral shRNA vector targeting CypD (shCypD) or scrambled control (shSCR). H–K) The CypD expression level (H, I) and HEV viral RNA level (J, K) were analyzed by real-time qPCR in stable CypD knockdown or SCR control cells. The data are means ± sem, of results in 4 independent experiments, normalized to GAPDH. **P < 0.01, ***P < 0.001 vs. shSCR (set as 1).