595   Common Molecular Marker in Progenitor Cells from CNS and Hematopoietic Progenitor Cells during JCV Infection.

M. C. G. Monaco-Kushner*, C. A. Messam, S. Frye, J. Hou, and E. O. Major.
Lab. of Molecular Med. and Neuroscience, NINDS, NIH, Bethesda, MD.

Background:JCV is a human polyomavirus that is able to infect cells of the brain such as oligodendrocytes and astrocytes, as well as hematopoietic progenitor cells and mature B-lymphocytes of the immune system. Although JCV binds to the surface of several cell types, susceptibility to infection appears to depend on the availability of cellular factors within target cells.

Methods:In this study we identified analogies between the CNS and the immune system and a common molecular marker that could play a key role in determining susceptibility to JCV infection. CD34⁺hematopoietic precursor cells and nestin⁺CNS progenitor cells are susceptible to JCV infection.

Results:When CNS progenitor cells were differentiated into glial cells, they retained susceptibility to JCV infection. However, when differentiated into neurons they were no longer susceptible. Likewise, CD34⁺hematopoietic progenitor cells were susceptible to JCV infection when differentiated into lymphoid cells but were no longer susceptible when differentiated, using PMA, into macrophage-like cells. We investigated the role of NF-1, a family of transcription proteins, during cell differentiation and the possible correlation with the loss of susceptibility to JCV infection. Several binding sites for NF-1 proteins characterize the regulatory sequence of JCV. Using a gel mobility shift assay, we detected the induction of NF-1—DNA complexes during PMA treatment of CD34⁺cell, but not in the control cells. Transfection of NF-1 class D DNA into the PMA-treated cells resulted in the re-establishment of susceptibility to JCV.

Conclusions:These data show that the expression of NF-1 class D is modulated during PMA-induced differentiation in the hematopoietic progenitor cel, and that high-level expression of this class restores susceptibility of these cells to JCV infection.

Therefore, selective expression of NF-1 class D may correlate with successful JCV infection in cells of the brain and immune system.