Host desmosomal proteins interacting with human parvovirus B19 genomic DNA.

Abstract

Human parvovirus B19 (B19V) primarily targets erythroid progenitor cells and is associated with various hematological disorders. However, the detailed mechanisms underlying its life cycle, particularly the viral assembly process, remain largely unknown. In this study, we used in vitro engineered DNA-binding molecule-mediated chromatin immunoprecipitation (in vitro enChIP) to identify host proteins associated with the B19V genome in infected UT7/Epo-S1 cells. Using guide RNAs targeting the viral terminal hairpin region, we successfully enriched viral genomic DNA. Mass spectrometry analysis of the precipitated fractions revealed specific enrichment of desmosomal proteins, including desmoplakin (DSP), desmoglein-1, desmocollin-1, and junction plakoglobin, suggesting that the components of the entire desmosome complex may be associated with the B19V genome. Immunofluorescence microscopy showed that the viral VP2 protein was strongly localized to the extranuclear foci, where it colocalized with DSP. Pull-down assays further demonstrated that VP2, but not VP1, interacted with DSP, indicating that the VP1-unique N-terminal region (VP1u) may inhibit this interaction. Notably, B19V-infected cells displayed reduced cell-cell adhesion and diminished cellular aggregation, implying that these interactions may be involved in the disruption of cell adhesion during infection. These findings revealed a novel mechanism by which B19V exploits the host desmosomal machinery to facilitate viral propagation in infected cells.