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.
Aiamkitsumrit
Benjamas
B
Drexel Institute for Biotechnology and Virology Research and Department of Microbiology and Immunology, College of Medicine, Drexel University, Doylestown, Pennsylvania, USA.
Zhang
Xianchao
X
Block
Timothy M
TM
Norton
Pamela
P
Fraser
Nigel W
NW
Su
Ying-Hsiu
YH
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D017353:Gene Deletion; D006561:Herpes Simplex / Q000473:pathology* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D007680:Kidney Neoplasms; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000821:virology*; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051381:Rats; D051996:Transcription Factor RelA / Q000378:metabolism; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics
D017874:Immediate-Early Proteins; D051996:Transcription Factor RelA; D014764:Viral Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D020932:Nerve Growth Factor; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1