Aiamkitsumrit Benjamas, Zhang Xianchao, Block Timothy M, Norton Pamela, Fraser Nigel W, Su Ying-Hsiu
Drexel Institute for Biotechnology and Virology Research and Department of Microbiology and Immunology, College of Medicine, Drexel University, Doylestown, Pennsylvania, USA.
J Neurovirol. 2007 Aug;13(4):305-14. doi: 10.1080/13550280701361490.
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.
有人提出，终末分化的神经元细胞和有丝分裂细胞在许多方面对单纯疱疹病毒1型（HSV-1）感染的反应不同。缺失ICP4、缺乏Us3的HSV-1突变株d120可在多种有丝分裂细胞系中诱导典型的凋亡。其在有丝分裂后细胞中的行为尚不清楚。在此，作者报告突变株d120病毒未能在神经元样、经神经生长因子（NGF）分化的PC12细胞中诱导凋亡。更引人注目的是，d120感染并未诱导凋亡，反而延长了培养瓶中不分裂的NGF分化PC12细胞的寿命。病毒基因组的半衰期为30天。与其他细胞（如Vero细胞）不同，野生型或d120感染NGF分化的PC12细胞均未诱导与病毒诱导凋亡相关的核因子（NF）-κB p65信号通路。因此，作者首次证明，与许多其他研究的细胞系不同，强效凋亡诱导突变株d120未能在神经元样NGF分化的PC12细胞中诱导凋亡。本文还讨论了d120未能在神经元样NGF分化的PC12细胞中诱导凋亡可能涉及的机制。
