Demonstration of different modes of cell death upon herpes simplex virus 1 infection in different types of oral cells.
The effects of Herpes simplex virus 1 (HSV-1) infection on five different types of oral cancerous cells (neck metastasis of gingival carcinoma (GNM) cells and tongue squamous cells of carcinoma (TSCCa) and non-cancerous cells (buccal mucosal fibroblasts (BF), gingival fibroblasts (GF), oral submucosal fibrosis cells (OSF)) and one type of non-oral cancerous cells (KB cells) were investigated. In HSV-1-infected cells the cell viability, CPE, viral antigens accumulation, caspase-3 activity, annexin V binding and DNA fragmentation were estimated. Three different forms or pathways of cell death were considered: apoptosis (the presence or rise of caspase-3 activity, DNA fragmentation and annexin V binding), slow cell death (the presence or rise of DNA fragmentation, the absence or decline of caspase-3 activity and annexin V binding), and necrosis (the absence of decline of caspase-3 activity, DNA fragmentation and annexin V binding). The viability of all cell types, except for KB cells, was reduced by the infection. CPE and viral antigens data demonstrated that all six types of cells could be infected with HSV-1. Upon HSV-1 infection there occurred (i) a classical apoptosis in GF cells, (ii) apoptosis in the early phase of infection and necrosis in the late phase of infection in GNM and TSCCa cells, (iii) slow cell death followed by necrosis in BF and OSF cells (however, these cells showed a different type of CPE), (iv) a classical slow cell death in KB cells. It is hypothesized that HSV-1 infection has a potential to induce several distinct pathways leading to cell death or several forms of cell death. Moreover, more than one pathway may be involved in the death of particular cell type. As HSV-1 was demonstrated to infect different oral and non-oral cells and cause different pathways or forms of cell death, the safety of using HSV-1 as a vector for gene therapy should be re-considered.
Huang
C R
CR
Institute of Immunology, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China.
Lin
S S
SS
Chou
M Y
MY
Ho
C C
CC
Wang
L
L
Lee
Y L
YL
Chen
C S
CS
Yang
C C
CC
D017304:Annexin A5 / Q000378:metabolism; D000956:Antigens, Viral / Q000032:analysis; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D053938:DNA Fragmentation; D005347:Fibroblasts / Q000821:virology; D005881:Gingiva / Q000166:cytology / Q000821:virology; D005887:Gingival Neoplasms / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007624:KB Cells; D009055:Mouth / Q000166:cytology / Q000821:virology*; D009061:Mouth Mucosa / Q000166:cytology / Q000821:virology; D009062:Mouth Neoplasms / Q000473:pathology / Q000821:virology*; D009336:Necrosis; D009914:Oral Submucous Fibrosis / Q000473:pathology / Q000821:virology*; D014062:Tongue Neoplasms / Q000473:pathology / Q000821:virology; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D000956:Antigens, Viral; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases