Structural Characterization of Human Bufavirus 1: Receptor Binding and Endosomal pH-Induced Changes

Area of Science:

• Virology
• Structural Biology
• Biochemistry

Background:

• Bufaviruses (BuV) are human parvoviruses causing acute diarrhea.
• Limited understanding of BuV disease mechanisms necessitates molecular and structural studies.
• No current treatment options exist for BuV infections.

Purpose of the Study:

• To investigate the BuV1 capsid's interaction with host cell receptors.
• To determine the structural basis of BuV1 entry and endo-lysosomal escape.
• To identify potential targets for antiviral drug development.

Main Methods:

• Glycan arrays and cell binding assays to identify BuV1 receptor.
• Cryo-electron microscopy (cryo-EM) to determine capsid structures at various pH.
• Biophysical assays to assess capsid stability during pH changes.

Main Results:

• BuV1 capsid binds terminal sialic acid (SIA) glycans.
• Cryo-EM structures reveal SIA binding at the 2/5-fold capsid surface.
• Conserved capsid residues stabilize SIA binding across human BuVs.
• BuV1 capsid is stabilized at endo-lysosomal pH (7.4-4) and destabilized at lower pH (≤3).
• Cryo-EM structures elucidate capsid rearrangements during endo-lysosomal escape.

Conclusions:

• BuV1 utilizes conserved sialic acid binding for host cell entry.
• Structural insights into pH-dependent capsid changes provide a mechanism for endo-lysosomal escape.
• The conserved SIA binding site is a potential target for novel antiviral therapies against bufaviruses.