Viral replication centers and the DNA damage response in JC virus-infected cells

Abstract

JCV is a human polyomavirus (PyV) that establishes a persistent infection in its host. Current immunomodulatory therapies, such as Natalizumab for multiple sclerosis, can result in JCV reactivation, leading to the debilitating brain disease progressive multifocal leukoencephalopathy (PML). JCV is among the viruses that recruit and modulate the host DNA damage response (DDR) to replicate its genome. We have identified host proteins recruited to the nuclear sites of JC viral DNA (vDNA) replication using three cell types susceptible to infection in vitro. Using confocal microscopy, we found that JCV recruited a similar repertoire of host DDR proteins to these replication sites previously observed for other PyVs. Electron tomography of JCV “virus factories” showed structural features like those described for murine PyV. These results confirm and extend previous observations for PyVs to JCV emphasizing a similar replication strategy among members of this virus family.