2. Academic Validation
  3. ARFGAP1 serves as a critical host factor during E30 infection: QS11 inhibits viral pathogenesis in hFcRn-IFNAR-/- mice

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

  • Virol J. 2025 Oct 29;22(1):351. doi: 10.1186/s12985-025-02971-9.
Jichen Li 1 2 3,  Wei Duan 1 2 3,  Ying Liu 1 2 3,  Rui Wang 1 2 3,  Qian Yang 1 2 3,  Huijie Li 1 2 3,  Yucai Liang 1 2 3,  Jinbo Xiao 1 2 3,  Jianfang Zhou 1,  Qiang Sun 4 5 6,  Yong Zhang 7 8 9
Affiliations

Affiliations

  • 1 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
  • 2 National Laboratory for Poliomyelitis, WHO WPRO Regional Polio Reference Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
  • 3 National Health Commission Key Laboratory of Microbial Genomics, National Health Commission Key Laboratory for Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
  • 4 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. sunqiang8611@126.com.
  • 5 National Laboratory for Poliomyelitis, WHO WPRO Regional Polio Reference Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. sunqiang8611@126.com.
  • 6 National Health Commission Key Laboratory of Microbial Genomics, National Health Commission Key Laboratory for Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. sunqiang8611@126.com.
  • 7 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. yongzhang75@sina.com.
  • 8 National Laboratory for Poliomyelitis, WHO WPRO Regional Polio Reference Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. yongzhang75@sina.com.
  • 9 National Health Commission Key Laboratory of Microbial Genomics, National Health Commission Key Laboratory for Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. yongzhang75@sina.com.
PMID: 41163005 DOI: 10.1186/s12985-025-02971-9
Abstract

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.

Keywords

ARFGAP1; CRISPR screening; Echovirus 30; QS11.

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