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Title: Intracellular Calcium Regulation in JC Polyomavirus Infection Authors: Ashley N. Soucy1,2, Jeanne K. DuShane2, Melissa S. Maginnis2 Affiliations: 1Honors College, 2Department of Molecular and Biomedical Sciences, University of Maine, Orono ME Background and Objectives: The majority of the human population is infected with JC polyomavirus (JCPyV). The virus establishes a persistent, asymptomatic infection in the kidney of healthy individuals. In immunosuppressed individuals, JCPyV can migrate to the CNS and cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). Previous studies suggested that calcium (Ca2+) signaling is necessary for the activation of transcription factors required for JCPyV infection. The goal of this study is to define how intracellular calcium flux influences the infectious life cycle and pathogenicity of the virus. Methods: Glial cells were pretreated with 2-APB, an antagonist of IP3-mediated Ca2+ release from the ER, or U73122, an inhibitor of PLC to prevent hydrolysis of PIP2 to IP3, then infected with JCPyV. Infection was quantified by indirect immunofluorescence microscopy. Cells treated with 2-APB were tested for the capacity to support virus binding by flow cytometry. Results: 2-APB inhibited JCPyV infection but had no effect on viral attachment, while U73122 resulted in reduced infection. Discussion and Conclusions: Inhibition of IP3-mediated Ca2+ release from the ER inhibits JCPyV infection in a dose-dependent manner, yet this inhibition had no effect on viral attachment. Inhibition of PLC, also reduces JCPyV infection. Taken together, these data suggest that Ca2+ release from the ER is required for JCPyV infection at a post-attachment step. Grant Support: Research reported in this project was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103423, a Frederick H. Radke Undergraduate Research Fellowship, and The University of Maine.