ARFGAP1 serves as a critical host factor during E30 infection: QS11 inhibits viral pathogenesis in hFcRn-IFNAR−/− mice

Echovirus 30 (E30) is a positive-sense RNA virus in the Picornaviridae family, specifically within the Enterovirus genu. It is a known pathogen that causes severe infectious diseases in humans. However, mechanisms underlying viral infection remain poorly understood. Therefore, this study aims to elucidate the mechanisms underlying E30 infection. A whole-genome CRISPR/Cas9 gene knockout screen was employed, and it was observed that knocking out ADP-ribosylation factor GTPase activating protein 1 (ARFGAP1) significantly reduced E30 replication. Subsequent analysis revealed that ARFGAP1 influencing the early stages and internalization of viral infection. Transcriptomic analysis further demonstrated that ARFGAP1 plays a crucial role in vesicular transport. Animal infection studies demonstrated that QS11-mediated inhibition of ARFGAP1 significantly decreased viral replication in mice with homozygous gene knock-out of both the human neonatal Fc receptor and the interferon-alpha/beta receptor (hFcRn-IFNAR^-/- mice), mitigated tissue damage, and enhanced survival rates. This study identifies ARFGAP1 as a crucial host factor that promotes E30 infection, offering in depth understanding of the viral infection mechanisms and potential antiviral therapies.