Completely conserved VP2 residue K140 of KREMEN1-dependent enteroviruses is critical for virus-receptor interactions and viral infection

• DOI: 10.1128/mbio.03040-24
• Publication Date: 2025-01-16T14:02:03Z
• Authors: Zeyu Liu; Xue Li; Xiaohong Li; Xingyu Yan; Yuan Tian; Yue Zhao; Kexin Liu; Pei Hao; Shuye Zhang; Chao Zhang
• Keywords: Viral infection; Residue (chemistry)

The KREMEN1 (KRM1) protein is a cellular receptor for multiple enteroviruses that cause hand, foot, and mouth disease (HFMD), including coxsackievirus CVA2, CVA3, CVA4, CVA5, CVA6, CVA10, CVA12. molecular basis the broad recognition of these viruses by KRM1 remains unclear. Here, we report indispensable role completely conserved VP2 capsid residue K140 (designated K2140) in mediating infection CVA10 other KRM1-dependent enteroviruses. Residue K2140 not only facilitates recognition, cell attachment, but also contributes to pathogenicity vivo. Notably, all strains Mutational analysis confirms importance CVA2-CVA6, Moreover, CVA8, an enterovirus which has yet been identified, possesses residue. We experimentally demonstrate CVA8 utilizes as its receptor, with being essential viral infection. Additionally, D90 engages plays crucial KRM1-mediated infections. Collectively, our findings underscore significance absolutely interactions KRM1-binding enteroviruses, providing novel insights into informing development broad-spectrum therapies against HFMD. Hand, (HFMD) annually affects millions children worldwide. HFMD caused various such coxsackieviruses CVA16, 71 (EV-A71). Licensed inactivated EV-A71 vaccines do provide cross-protection There are no drugs specifically serves many HFMD-related However, elusive. (K2140) among virus-receptor binding interacting KRM1. Overall, deeper understanding vitro vivo may contribute anti-enterovirus treatments.