JC polyomavirus-encoded miRNA jcv-miR-J1-5p downregulates BK polyomavirus infection

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• BK Polyomavirus (BKPyV) and JC Polyomavirus (JCPyV) are closely related viruses that establish persistent infections.
• JCPyV replication may prevent BKPyV-related pathologies in kidney transplant recipients.
• Viral microRNAs (miRNAs) are homologous between BKPyV and JCPyV, suggesting a role in interspecies competition.

Purpose of the Study:

• To investigate the mechanism by which JCPyV inhibits BKPyV replication in kidney transplant recipients.
• To determine the role of viral miRNAs in the observed competition between BKPyV and JCPyV.

Main Methods:

• Case-control study of 39 kidney transplant recipients to assess the association between urinary jcv-miR-J1-5p levels and BKPyV DNAemia.
• In vitro modeling using immortalized human renal proximal tubular epithelial cells to study JCPyV's effect on BKPyV growth.
• Engineering of an archetypal JCPyV strain to quench miRNA maturation to confirm the role of miRNAs in JCPyV's inhibitory effect.

Main Results:

• Early detection of urinary jcv-miR-J1-5p significantly reduced the risk of BKPyV DNAemia (OR=0.00 [0.00-0.65], p=0.012).
• In vitro, JCPyV infection reduced BKPyV growth without significant JCPyV protein expression.
• The JCPyV-specific miRNA jcv-miR-J1-5p decreased BKPyV TAg mRNA expression, similar to BKPyV-encoded miRNAs.

Conclusions:

• JCPyV-specific miRNA jcv-miR-J1-5p limits BKPyV infectivity and early TAg expression.
• This miRNA-mediated inhibition by JCPyV contributes to the in vivo competition observed between BKPyV and JCPyV infections.
• Viral miRNA cross-reactivity is a key mechanism explaining JCPyV's protective effect against BKPyV pathologies in kidney transplant recipients.