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A human hepatocarcinoma cell line, PLC/PRF/5, is susceptible to hepatitis E virus (HEV) infection and is used for isolating this virus. It is difficult to use this cell line for the isolation of HEV directly from fecal specimens of swine or wild boar contaminated with porcine sapelovirus (PSV), because PSV infection results in rapid and extensive cytopathic effects in PLC/PRF/5 cells, interrupting the growth of HEV. Herein, we used a PSV infection-resistant cell line, N1380 derived from PLC/PRF/5 cells, and we successfully isolated an HEV-4