A pUL25 dimer interfaces the pseudorabies virus capsid and tegument

Area of Science:

• Structural Biology
• Virology
• Molecular Biology

Background:

• Tegument proteins pUL25 and pUL36 are essential for alpha-herpesvirus virion assembly and intracellular capsid transport.
• Previous cryo-electron microscopy (cryoEM) studies lacked the resolution to define the precise organization and stoichiometry of pUL25 and pUL36 on the capsid.

Purpose of the Study:

• To determine the high-resolution structure of the capsid-tegument interface in alpha-herpesviruses.
• To resolve the controversial stoichiometry and organization of tegument proteins pUL25 and pUL36.

Main Methods:

• Three-dimensional (3D) icosahedral reconstruction of pseudorabies virus (PRV) using electron-counting cryo-electron microscopy (cryoEM).
• Achieved a resolution of 4.9 Å, enabling detailed structural analysis.

Main Results:

• Resolved a dimer of pUL25 forming a complex with pUL36 and pUL17 at the capsid vertices via a coiled coil helix bundle.
• Corrected previous misinterpretations regarding the organization of these key tegument proteins.
• Identified conserved and distinct features in the capsid-tegument interface between alpha-herpesviruses (PRV) and gamma-herpesviruses (KSHV).

Conclusions:

• The study provides a corrected model for the capsid-associated tegument complex in alpha-herpesviruses.
• This detailed structural information is critical for understanding herpesvirus assembly and pathogenesis.
• Comparative analysis highlights subfamily-specific differences in herpesvirus architecture.