The following is a summary of “Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation Patients,” published in the April 2023 issue of Infectious Diseases by Leuzinger, et al.
BK polyomavirus (BKPyV) replication in allogeneic hematopoietic cell transplantation (HCT) is associated with failing immune control and BKPyV-associated hemorrhagic cystitis. However, molecular markers of BKPyV replication and disease must be better understood.
To identify these markers, 20 HCT patients were studied longitudinally using quantitative nucleic acid testing (QNAT), DNase-I treatment before QNAT, next-generation sequencing (NGS), and cell-mediated immunity testing.
The study found that larger QNAT amplicons led to under-quantification and false-negative results (P < .001). DNase-I reduced urine and plasma BKPyV-loads by >90% (P < .001), indicating non-encapsidated BKPyV genomes. However, DNase-resistant urine BKPyV-loads remained infectious in cell culture. BKPyV genome fragmentation of ≤250 bp impaired NGS coverage of genetic variation using 1,000-bp and 5,000-bp amplicons. Conversely, 250-bp amplicons captured viral minority variants.
The study also identified genotype-specific and genotype-independent changes in capsid Vp1 or T-antigen predicted to escape from antibody neutralization or cytotoxic CD8 T-cells, respectively. Genotype-specific changes in immunodominant 9mers were associated with reduced or absent CD8 T-cell responses. The findings suggested that failure to control BKPyV replication in HCT patients may involve insufficient genotype-specific cytotoxic CD8 T-cell responses, potentially predictable by low neutralizing antibodies and genotype-independent immune escape.
The study’s results provided new insights for patient evaluation and designing immune protection strategies, such as neutralizing antibodies, adoptive T-cell therapy, or vaccines.