Single-Cell Transcriptomics Reveals a Heterogeneous Cellular Response to BK Virus Infection

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• BK virus (BKV) is a human polyomavirus causing disease in immunosuppressed individuals, particularly kidney transplant recipients.
• BKV infection in renal cells can lead to significant complications.
• Previous bulk analyses showed BKV upregulates cell proliferation genes but few downregulated genes.

Purpose of the Study:

• To investigate viral and cellular transcript dynamics in single BKV-infected human renal proximal tubule epithelial (RPTE) cells.
• To identify distinct cellular responses to BKV infection at the single-cell level.
• To uncover previously unidentified pathways downregulated by BKV.

Main Methods:

• Single-cell transcriptomics (RNA-seq) of mock- or BKV-infected primary human RPTE cells.
• Analysis of viral mRNA and protein expression levels in individual cells.
• Comparison of cellular gene expression patterns between cells with high and low viral loads.

Main Results:

• Viral mRNA and protein expression varied significantly among infected cells.
• A minority (approx. 20%) of infected cells exhibited high viral transcript levels and distinct gene expression patterns.
• Cells with low viral mRNA did not progress to high expression, suggesting early determination of cellular response.
• BKV downregulated previously unidentified pathways, including drug metabolism, TNF signaling, energy metabolism, and translation, particularly in highly infected cells.

Conclusions:

• Single-cell transcriptomics reveals heterogeneous BKV infection outcomes, with a subset of cells supporting high viral replication.
• BKV manipulates specific cellular pathways, including drug metabolism and immune signaling, potentially to evade host defenses or limit infection.
• Understanding these single-cell responses is crucial for comprehending BKV pathogenesis and developing therapeutic strategies.