The Conserved YPX₃L Motif in the BK Polyomavirus VP1 Protein Is Important for Viral Particle Assembly but Not for Its...

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• BK polyomavirus (BKPyV) infection is usually asymptomatic but can reactivate under immunosuppression, causing severe complications like nephropathy in kidney transplant recipients.
• BKPyV virions utilize extracellular vesicles for intercellular trafficking, enabling cell exit without lysis and diverse entry routes into target cells.

Purpose of the Study:

• To investigate if BKPyV virions recruit the Endosomal-Sorting Complexes Required for Transport (ESCRT) machinery via late domains to hijack extracellular vesicles.
• To determine the role of a specific YPX3L motif in the BKPyV VP1 protein in this process.

Main Methods:

• Comparison with other naked viruses to understand BKPyV's mechanism.
• Creation and analysis of BKPyV pseudovirions with specific point mutations in the VP1 protein.
• Studying mutations from clinical isolates and those known to disrupt ESCRT machinery interaction.

Main Results:

• A single potential late domain (YPX3L motif) was identified in the BKPyV VP1 protein.
• Mutations in this motif did not affect BKPyV's association with extracellular vesicles.
• However, these mutations were found to be critical for capsomere interaction and subsequent viral particle assembly.

Conclusions:

• The identified YPX3L motif in BKPyV VP1 is essential for viral assembly, not for hijacking extracellular vesicles.
• This finding clarifies a key aspect of BKPyV replication and pathogenesis, particularly in immunosuppressed individuals.