BK Polyomavirus Diversity After Hematopoietic Stem Cell Transplantation

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• BK polyomavirus (BKPyV) infection is a frequent complication post-hematopoietic stem cell transplantation (HSCT).
• BKPyV is associated with hemorrhagic cystitis (HC) development, but its precise role in pathogenesis remains unclear.
• Understanding BKPyV diversity is crucial for managing post-HSCT complications.

Purpose of the Study:

• To investigate the impact of BKPyV genetic diversity on the development of HC in pediatric HSCT patients.
• To analyze BKPyV subtypes and viral loads in relation to HC incidence.
• To identify mutation patterns within BKPyV genomes associated with HC.

Main Methods:

• Analysis of 147 urine samples from pediatric HSCT patients with quantifiable BKPyV at 1 month post-transplant.
• Amplification of BKPyV DNA using in-house polymerase chain reaction (PCR).
• Next-generation sequencing (NGS) of BKPyV to determine subtypes and analyze protein-coding regions.

Main Results:

• Subtype Ia was the most prevalent BKPyV subtype (61.3%), followed by subtype Ib1 (31.4%).
• Median viral load for subtype Ia was significantly higher than for subtype Ib1 at 1 month post-HSCT.
• APOBEC-induced mutations and specific mutation signatures associated with HC were identified across BKPyV protein-coding regions.

Conclusions:

• BKPyV subtype Ia may play a more significant role in HC development post-HSCT due to higher viral loads.
• Genetic diversity and mutation patterns within BKPyV are associated with HC pathogenesis.
• This study provides the largest BKPyV sequencing dataset from a single HSCT cohort, valuable for future research.