The neonatal Fc receptor (FcRn): Guardian or Trojan Horse in viral infection?

The neonatal Fc receptor (FcRn), well-known for mediating the transfer of maternal immunoglobulin G (IgG) to neonates, plays a critical role in neonatal antimicrobial defenses. Furthermore, FcRn regulates IgG and albumin homeostasis via pH-dependent recycling pathways, thereby prolonging their plasma half-life in circulation. FcRn also enables bidirectional transcytosis of antibodies across cellular barriers, a function essential for maintaining humoral immunity. However, recent studies have demonstrated that some viruses exploit FcRn to facilitate viral infection, underscoring its dual role in the viral lifecycle. This review aims to comprehensively discuss the dual functions of FcRn during viral infections, with particular focus on how diverse viruses utilize FcRn to promote infection. Here, we summarize the molecular mechanisms underlying FcRn-mediated proviral processes, including viral uncoating, transcytosis, and antibody-dependent enhancement (ADE) of infection. Finally, we propose potential therapeutic strategies targeting FcRn to inhibit viral replication.