Herpes simplex virus type 1 ICP4 deletion mutant virus d120 infection failed to induce apoptosis in nerve growth factor-differentiated PC12 cells.

It has been suggested that terminally differentiated neuronal cells and mitotic cells respond differently in many aspects to herpes simplex virus type 1 (HSV-1) infection. The ICP4-deleted, Us3-defective, HSV-1 mutant strain d120 induces classical apoptosis in a variety of mitotic cell lines. Its behavior in postmitotic cells is not known. Here the authors report that mutant d120 virus failed to induce apoptosis in neuronal-like, nerve growth factor (NGF)-differentiated PC12 cells. More strikingly, rather than inducing apoptosis, d120 infection prolonged the life of nondividing NGF-differentiated PC12 cells in the culture flask. The virus genome had a half-life of 30 days. Unlike in other cells, such as Vero, neither wild-type nor d120 infection of NGF-differentiated PC12 cells induced the nuclear factor (NF)-kappa B p65 pathway, which has been associated with virus-induced apoptosis. Thus, the authors demonstrate, for the first time, that a potent apoptosis inducer mutant d120 failed to induce apoptosis in neuronal-like NGF-differentiated PC12 cells, unlike a number of other cell lines studied. The possible mechanisms involved in the failure of d120 to induce apoptosis in neuronal-like NGF-differentiated PC12 cells are discussed.