Structures of Echovirus 30 in complex with its receptors inform a rational prediction for enterovirus receptor usage

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Viral receptor usage dictates cell tropism and classification, closely correlating with virus structure.
• Enterovirus B (EV-B) comprises subgroups based on receptor usage; echovirus 30 (E30) uses FcRn, a common cause of aseptic meningitis.
• Receptors for many enteroviruses (EVs) remain unidentified, hindering understanding of viral entry and tropism.

Purpose of the Study:

• To analyze the atomic structures of E30 virions and related particles to understand receptor binding.
• To elucidate the molecular basis of E30 receptor recognition by FcRn and CD55.
• To develop a structure-based computational method for predicting EV receptor usage.

Main Methods:

• Cryo-electron microscopy was used to determine the atomic structures of E30 mature, empty, and A-particles.
• Structures of E30 complexed with FcRn and CD55 were obtained and analyzed.
• Comparative structural analysis with homologous viruses and experimental receptor data were integrated.

Main Results:

• Distinct serotype-specific epitopes and conformational differences were observed within EV-B subgroups.
• The VP1 BC loop was identified as a distinguishing structural marker for E30 within EV-B.
• The molecular mechanisms of E30 binding to FcRn and CD55 were deciphered.
• A structure-based in silico algorithm for predicting EV receptor usage was developed.

Conclusions:

• Structural analysis reveals key differences and receptor binding mechanisms for E30.
• The VP1 BC loop serves as a potential structural marker for EV-B classification.
• The developed algorithm offers a rational approach for predicting enterovirus receptor tropism.