Low pH-induced conformational change in herpes simplex virus glycoprotein B

Area of Science:

• Virology
• Cell Biology
• Structural Biology

Background:

• Herpesviruses utilize pH-dependent endocytosis for host cell entry.
• Envelope glycoprotein B (gB) is essential for mediating membrane fusion and viral entry across all herpesviruses.

Purpose of the Study:

• To investigate the effect of pH on the conformation and function of herpes simplex virus (HSV) glycoprotein B (gB).
• To elucidate the role of pH-induced conformational changes in gB during herpesviral entry.

Main Methods:

• Studied conformational changes in HSV gB upon exposure to mildly acidic pH in vitro and during cell entry.
• Analyzed alterations in gB's antigenic structure and oligomeric state using biophysical techniques.
• Investigated the properties of purified, recombinant gB under acidic conditions.

Main Results:

• Mildly acidic pH triggers specific conformational changes in HSV gB, altering its antigenic structure and oligomeric conformation.
• Low pH exposure converts virion gB into a lower-order oligomer, a reversible process.
• Acidic pH increases the hydrophobicity of purified gB, indicating direct pH-induced alterations.

Conclusions:

• Intracellular low pH induces critical alterations in gB conformation, facilitating virion-cell fusion.
• These pH-dependent conformational changes in gB, alongside receptor binding, are essential for herpesviral entry via endocytosis.