Exploring a Novel Myeloid Subset for Transporting Polyomavirus to the CNS

Abstract JC polyomavirus (JCPyV) is the causative agent of the often-fatal demyelinating brain disease Progressive multifocal leukoencephalopathy (PML). While 70-90% of adults carry JCPyV lifelong, only after immunosuppression is the virus able to travel from the primary infection reservoir in the urinary tract to the central nervous system. How the virus traffics to and enters the brain is unknown. Utilizing the mouse polyomavirus (MuPyV), a natural mouse pathogen, I have employed Fluorescence-activated cell sorting (FACS), RT-qPCR, flow cytometry, and immunofluorescent imaging to phenotype a subset of macrophages with activity replicating MuPyV. These macrophages are express CD13 and are found in the spleen, brain, and blood. These CD13+ myeloid cells possess unique expression of surface markers compared to other macrophages in the tissues. Notably, CD13- macrophages do not support MuPyV infection. Our published data suggests that the ependyma, a multi-ciliated single-cell layer lining the cerebral ventricles, may be a site of entry into the brain parenchyma. Our lab has found that the ependyma supports productive MuPyV infection. The ependyma is contiguous with the choroid plexus epithelium, which supports JCPyV infection. By immunofluorescence microscopy, I visualized CD13+ macrophages at the ependyma in uninfected mice. Monocytes/macrophages enter at this blood-CSF barrier as part of cell population homeostasis. I have found that CD13+ monocytes also selectively support MuPyV infection. These results together suggest that CD13+ macrophages are a candidate for MuPyV trafficking to the central nervous system.