pH-Induced Conformational Changes of Human Bocavirus Capsids

Area of Science:

• Structural biology
• Virology
• Molecular mechanisms of viral infection

Background:

• Human bocaviruses (HBoVs) cause respiratory and gastrointestinal infections in vulnerable populations.
• Lack of suitable models hinders HBoV treatment and vaccine development.
• Capsid structure variations influence HBoV tissue tropism and antigenicity.

Purpose of the Study:

• Determine the cryo-electron microscopy structure of HBoV2 at neutral pH (7.4) and compare it with HBoV1, HBoV3, and HBoV4.
• Analyze the cell surface glycan-binding properties of HBoV1 and HBoV2.
• Investigate structural changes in HBoV1 and HBoV2 capsids at acidic pH (5.5 and 2.6) relevant to infection.

Main Methods:

• Cryo-electron microscopy and image reconstruction to determine viral capsid structures.
• Biochemical analysis of glycan-binding characteristics.
• Comparative structural analysis of HBoV strains under varying pH conditions.

Main Results:

• HBoV2 capsid structure determined at 2.7 Å resolution, showing similarity to other gastrointestinal HBoVs (HBoV2-4) but differing from respiratory HBoV1 in surface variable region III.
• HBoV1 and HBoV2 do not attach to cells via common glycans (sialic acid, galactose, GlcNAc, heparan sulfate).
• Acidic pH induces conformational changes in HBoV1 and HBoV2 capsids, particularly at the VP N-terminus and specific surface loops, suggesting a mechanism for viral entry.

Conclusions:

• Structural similarities in VR III correlate with tissue tropism among HBoV strains.
• Capsid conformational changes at low pH are crucial for HBoV trafficking and infection.
• These findings provide a molecular basis for understanding HBoV infection dynamics and developing control strategies.