Infection of murine oligodendroglial precursor cells with Human Herpesvirus 6 (HHV-6) — establishment of a murine in vitro model

BackgroundHuman Herpesvirus 6 was previously demonstrated to infect human oligodendroglial precursor cells (OPCs) in vitro causing cell cycle arrest and premature differentiation with consequent loss of the precursor pool.ObjectivesTo develop an in vitro murine OPC model to study the cell cycle and differentiation effects of HHV-6 in more readily available, genetically well-defined cells free of the risk of contamination with human herpesviruses.Study designMurine OPCs were exposed to infectious HHV-6A or HHV-6B and analyzed for production of viral transcripts, particles, and replicating virus. FACS analysis and specific markers were used to evaluate effects on cell cycling and differentiation.ResultsHHV-6 infection of murine OPCs resulted in production of both immediate-early and some late transcripts but no replicating virus by TaqMan quantitative PCR or electron microscopy. Both a specific G1/S cell cycle arrest and premature loss of OPCs through differentiation into oligodendrocytes as previously seen with human precursors were recapitulated.ConclusionsInfection of murine OPCs by HHV-6 reproduces the critical phenotypes of cell cycle arrest and altered differentiation seen in human cells. The murine system provides a highly defined, accessible, and reproducible source of cells permitting the elucidation of specific viral and cell cycle genes involved in CNS viral infections of OPCs.