mk-2206 and Leukoencephalopathy--Progressive-Multifocal

Progressive multifocal leukoencephalopathy (PML) is an often-fatal demyelinating disease of the central nervous system. PML results when oligodendrocytes within immunocompromised individuals are infected with the human JC virus (JCV). We have identified an oligodendrocyte precursor cell line, termed G144, that supports robust levels of JCV DNA replication, a central part of the JCV life cycle. In addition, we have determined that JC virus readily infects G144 cells. Furthermore, we have determined that JCV DNA replication in G144 cells is stimulated by myristoylated (i.e., constitutively active) Akt and reduced by the Akt-specific inhibitor MK2206. Thus, this oligodendrocyte-based model system will be useful for a number of purposes, such as studies of JCV infection, establishing key pathways needed for the regulation of JCV DNA replication, and identifying inhibitors of this process.

Topics: Cell Line; DNA Replication; DNA, Viral; Heterocyclic Compounds, 3-Ring; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Oligodendroglia; Oncogene Protein v-akt; Virus Replication