Poster Sessions

V -22

Maria Chiara Monaco

M. C. G. Monaco, D. Maric, E. O. Major

Human neural progenitor-derived oligodendrocytes and JCV infection

Cultures of human neural progenitor cells are capable of proliferating in vitro while maintaining the potential to give rise to the major neural phenotypes, neurons, astrocytes and oligodendrocytes. We previously demonstrated that primary human brain derived progenitor cells could be differentiated using selective cell culture conditions into progenitor-derived-neurons (PDN) and progenitor-derived-astrocytes (PDA). We have now refined this cell culture model to direct the growth and differentiation of progenitor cells toward progenitor-derived oligodendrocytes (PDO). Successful differentiation into this lineage was demonstrated by the expression of specific markers such as A2B5, O4, GalC (galactocerebroside) and MBP (myelin basic protein). These cell culture models are highly useful for the study of cellular tropism of the human polyomavirus, JCV, restricted in its multiplication in the adult brain to the oligodendrocyte. JCV lytic infection of oligodendrocytes in immune compromised adults results in the demyelinating disease progressive multifocal leukoencephalopathy. We therefore tested JCV infection in PDOs selected for expression of the viral receptor alpha 2-6 linked sialic acid (SA) with or without expression of a co-receptor, 5HT2A, the serotonin receptor. Only low levels of JCV infectivity could be seen in the PDOs in comparison to highly productive infection in PDAs and tonsillar stromal cells, both cell types known to support JCV multiplication in cell culture. Presence of the 5HT2A serotonin receptor did not increase PDO susceptibility to JCV.