Effect of hexamethylene bisacetamide and cyclosporin A on recovery of herpes simplex virus type 2 from the in vitro model of latency in a human neuroblastoma cell line.
The goal of the present work was to examine whether hexamethylene bisacetamide (HMBA) and cyclosporin A affect the recovery of herpes simplex virus type 2 (HSV-2) from an in vitro model of HSV-2 latency in human neuroblastoma cell line IMR-32. IMR-32 cells were infected with HSV-2 at a multiplicity of infection of 0.1 plaque-forming units/cell and were cultured at 40 degrees C for 14 days, resulting in the establishment of a model of HSV-2 latency in IMR-32 cells. When the cultivation temperature was shifted down from 40 to 37 degrees C, recovery of virus growth began to occur after an incubation period of 2 days. During the time of shift-down of the incubation temperature, the latently infected cells were further cultured at 37 degrees C in the presence or absence of 5 mM HMBA or 0.5 micrograms/ml cyclosporin A, which does not affect stability of HSV-2 nor proliferation of IMR-32 cells. Consequently, the rate of HSV-2 recovery from the latently infected cells cultured in the presence of 5 mM HMBA was significantly increased, as compared with the untreated controls. In addition, the DNA methylation level of the latently infected IMR-32 cells cultured in the presence of HMBA was significantly decreased when compared to the level in the untreated controls. On the other hand, the cultivation of the latently infected cells in the presence of 0.5 micrograms/ml cyclosporin A resulted in a significant decrease in the rate of HSV-2 recovery. These findings indicate that the recovery of HSV-2 from the model of latency in IMR-32 cells is enhanced by HMBA treatment, which induces a significant decrease of total genomic DNA methylation level, and is inhibited by cyclosporin A treatment.
Kondo
Y
Y
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Japan.
Yura
Y
Y
Iga
H
H
Yanagawa
T
T
Yoshida
H
H
Furumoto
N
N
Sato
M
M
D000081:Acetamides / Q000494:pharmacology*; D002460:Cell Line; D003524:Cyclosporins / Q000494:pharmacology*; D004279:DNA, Viral / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma; D015183:Restriction Mapping; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D000081:Acetamides; D003524:Cyclosporins; D004279:DNA, Viral; C014026:hexamethylene bisacetamide