Objective: Varicella zoster virus (VZV) can spread anterogradely and infect cerebral arteries causing VZV vasculopathy and arterial ischaemic stroke (AIS). In this study we tested the hypothesis that virus-infected cerebrovascular fibroblasts undergo phenotypic changes that promote vascular remodeling and facilitate virus transmission in an in vitro model of VZV vasculopathy. The aims of this project were therefore: (i) to examine the changes that virus-infected Human brain adventitial vascular fibroblasts (HBVAF) undergo in an in vitro model of VZV vasculopathy; and to (ii) identify disease biomarkers relating to VZV related vasculopathy. Methods: HBVAF were infected with VZV, and their ability to migrate, proliferate, transdifferentiate and interact with endothelial cells was studied with flow cytometry. Microparticles (MP) released from these cells were isolated, and imaged with transmission electron microscopy; and their protein content analysed with mass spectrometry. Circulating MP profiles were also studied in children with VZV and non-VZV vasculopathy and compared with controls. Results: VZV-infected HBVAF transdifferentiated into myofibroblasts with enhanced proliferative and migratory capacity. Interaction of VZV-infected HBVAF with endothelial cells resulted in endothelial dysfunction. These effects were, in part, mediated by the release of MP from VZV infected HBVAF. These MP contained VZV virions that could transmit VZV to neighbouring cells, highlighting a novel model of VZV cell-to-cell viral dissemination. MP positive for VZV were significantly higher in children with VZV-related vasculopathy compared to children with non-VZV vasculopathy (p=0.01), and controls (p=0.007). Conclusions: VZV infected HBVAF promote vascular remodeling and facilitate virus transmission. These effects were mediated by the release of apoptotic MP that could transmit VZV infection to neighbouring cells, through a “Trojan Horse” means of productive viral infection. VZV+MP may represent a disease biomarker worthy of further study.