Repair replication of viral and cellular DNA in herpes simplex virus type 2-infected human embryonic and xeroderma pigmentosum cells

Abstract

When human embryonic fibroblasts were infected with herpes simplex virus type 2 (HSV-2) at a multiplicity of 5 PFU/cell, repair replication of cellular DNA was detectable by 3–5 hr postinfection (p.i.). Between 12 and 14 hr p.i., predominantly repair replication of cellular DNA was noted but some repair and semiconservative replication of viral DNA occurred. Almost all DNA synthesis between 22 and 24 hr p.i. was derived from repair synthesis of cellular and viral DNA. Alkaline sucrose gradient sedimentation analysis revealed that cellular DNA of HSV-2-infected cells suffered extensive strand breaks by 14 hr p.i. Significant repair replication of cellular DNA was induced by HSV-2 even in the presence of 100 μg/ml of phosphonoacetic acid which inhibits viral DNA synthesis to undetectable levels. Repair replication of cellular and viral DNA was also detected in infected xeroderma pigmentosum (XP12BE) cells. The results suggest that HSV-2 induced repairable damage in cellular DNA without viral DNA replication and that native HSV-2 DNA which accumulated in the infected cells had a repairable structure (probably strand breaks) that did not require incision for repair.