# The Conserved YPX3L Motif in the BK Polyomavirus VP1 Protein Is Important for Viral Particle Assembly but Not for Its Secretion into Extracellular Vesicles

## TL;DR

This study investigates a specific protein motif in BK polyomavirus and finds it important for virus assembly but not for its release via extracellular vesicles.

## Contribution

The study identifies the role of a conserved YPX3L motif in BKPyV VP1 for viral assembly, not extracellular vesicle secretion.

## Key findings

- The YPX3L motif in BKPyV VP1 is crucial for viral particle assembly.
- The motif is not involved in the virus's secretion into extracellular vesicles.
- Mutations in the motif affect capsomere interactions but not vesicle association.

## Abstract

The BK polyomavirus (BKPyV) is a small DNA non-enveloped virus whose infection is asymptomatic in most of the world’s adult population. However, in cases of immunosuppression, the reactivation of the virus can cause various complications, and in particular, nephropathies in kidney transplant recipients or hemorrhagic cystitis in bone marrow transplant recipients. Recently, it was demonstrated that BKPyV virions can use extracellular vesicles to collectively traffic in and out of cells, thus exiting producing cells without cell lysis and entering target cells by diversified entry routes. By a comparison to other naked viruses, we investigated the possibility that BKPyV virions recruit the Endosomal-Sorting Complexes Required for Transport (ESCRT) machinery through late domains in order to hijack extracellular vesicles. We identified a single potential late domain in the BKPyV structural proteins, a YPX3L motif in the VP1 protein, and used pseudovirions to study the effect of point mutations found in a BKPyV clinical isolate or known to ablate the interaction of such a domain with the ESCRT machinery. Our results suggest that this domain is not involved in BKPyV association with extracellular vesicles but is crucial for capsomere interaction and thus viral particle assembly.