Remodeling of the cellular membrane architecture in response to BK polyomavirus infection

BK polyomavirus (BKPyV) is a human pathogen that causes severe disease in immunocompromised individuals. Although discovered in the 1970s, important gaps in our understanding of BKPyV biology persist. Key unresolved areas include the precise molecular mechanisms governing viral latency and reactivation, the specific host and viral factors determining the virus tropism towards the urinary track, and the intricate virus-host interactions that drive clinical pathogenesis. These unresolved biological questions have stalled the development of targeted therapeutics; as a result, no specific antiviral therapy is currently available for BKPyV-related diseases. In this review, we examined findings from both experimental models and clinical samples that investigate how BKPyV remodels host organelles and the molecular pathways underlying these alterations. We focus on BKPyV-driven changes in cellular membranes, including endoplasmic reticulum remodeling, mitochondrial disruption, the formation of endoplasmic reticulum-derived tubuloreticular structures, vacuoles, and autophagosomes, as well as the accumulation of lipid droplets. Collectively, these organelle-specific modifications highlight membrane remodeling as a central feature of BKPyV replication and pathogenesis. Addressing the key knowledge gaps in the molecular basis of virus-induced membrane remodeling will be critical for guiding the development of effective antiviral strategies.