Frequent Infection of Cortical Neurons by JC Virus in patients with Progressive Multifocal Leukoencephalopathy

摘要

The human polyomavirus JC (JCV) infects glial cells and causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, in immunosuppressed individuals. The extent of JCV infection of neurons is unclear. We determined the prevalence and pattern of JCV infection in grey matter (GM) by immunostaining in archival brain samples of 49 PML patients and 109 control subjects. Among PML patients, 96% had demyelinating lesions in white matter and at the grey-white junction (GWJ); 57% had them in the GM. Most JCV-infected cells in GWJ and GM were glia but JCV infected neurons in PML lesions at the GWJ of 54% and GM of 50% patients, and in GM outside of areas of demyelination in 11% of patients. JCV regulatory T antigen (Ag) was expressed more frequently in cortical neurons than the VP1 capsid protein. None of the control subjects without PML had any cells expressing JCV proteins. Thus, the cerebral cortex often harbors demyelinating lesions of PML and JCV infection of cortical neurons is frequent in PML patients. The predominance of T Ag over VP1 expression suggests a restrictive infection in neurons. These results indicate that JCV infection of cerebral cortical neurons is a previously under-appreciated component of PML pathogenesis.