Herpes simplex virus induces unscheduled DNA synthesis in virus-infected cervical cancer cell lines

We evaluated herpes-simplex-virus-type-2(HSV2)-induced unscheduled DNA synthesis in virus-infected cervical cancer (HeLa, CaSki, C-33A, and SiHa) cells. HSV2 replication was approximately 100-fold more efficient in the HeLa cells than in less susceptible C-33A and SiHa cells. In dual parameter flow cytometric analysis of bromodeoxyuridine (BrdU) incorporation, HSV2-infected HeLa cells showed a rapid increase in the proportions of DNA-synthesizing G1- and S-phase cells, whereas in C-33A and SiHa cells, the proportions of DNA-synthesizing G1- and early S-phase cells were increased late in the infection. Blocking of HSV2 replication by phosphonoformate inhibited virus-induced changes in HeLa cells, but not in C-33A and SiHa cells. Anti-BrdU antibodies exhibited a coarse globular nuclear staining pattern in the C-33A cells, while the other cells showed speckled and/or fine globular nuclear fluorescence. Anti-ICP8 (HSV-specified major DNA-binding protein) antibodies revealed that, in C-33A cells, ICP8 remained in the cytoplasm, whereas in the other cells, speckled or globular nuclear fluorescence was found. Our results showed that HSV2 induced the unscheduled synthesis of cellular DNA, which was host-cell-dependent, and in virus infected C-33A cells, it may be attributable to both viral and cellular proteins.