biostudies-literatureUnknown35(1)Chen BEnterovirus A71 (EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-α (IFN-α) has been used in antiviral therapy for decades; it has been reported that EV-A71 antagonizes the antiviral activity of IFN-α based on viral 2A^pro-mediated reduction of the interferon-alpha receptor 1 (IFNAR1); however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-α in RD cells, whereas EV-A71 infection caused obvious down-regulation of the IFNAR1 protein and blockage of IFN-α signaling. Subsequently, we observed that EV-A71 2A^pro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4GI (eIF4Virologica Sinica64-72https://www.ebi.ac.uk/biostudies/studies/S-EPMC7035401biostudies-literatureCellular Caspase-3 Contributes to EV-A71 2A^pro-Mediated Down-Regulation of IFNAR1 at the Translation Level.PMC7035401Peng YWang SZhang HPei XWang YChen BfalseCellular Caspase-3 Contributes to EV-A71 2A^pro-Mediated Down-Regulation of IFNAR1 at the Translation Level.Enterovirus A71 (EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-α (IFN-α) has been used in antiviral therapy for decades; it has been reported that EV-A71 antagonizes the antiviral activity of IFN-α based on viral 2A^pro-mediated reduction of the interferon-alpha receptor 1 (IFNAR1); however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-α in RD cells, whereas EV-A71 infection caused obvious down-regulation of the IFNAR1 protein and blockage of IFN-α signaling. Subsequently, we observed that EV-A71 2A^pro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4GI (eIF42020-01-01T00:00:00Z2020 Feb2025-04-21T18:01:07.892Z2020-09-14T07:17:24ZS-EPMC70354013151210610.1007/s12250-019-00151-y