G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV

Madireddy, Advaitha; Purushothaman, Pravinkumar; Loosbroock, Christopher P.; Robertson, Erle S.; Schildkraut, Carl L.; Verma, Subhash C.

Further, we show that stalling of replication forks is accompanied by a reduction in episomally maintained viral genome copies in PhenDC3 treated KSHV infected cells. More importantly, the KSHV genome copy number remained low even upon withdrawal of the PhenDC3 compound and the continued growth of the cells in drug-free medium. Our data conclusively demonstrates that treatment with PhenDC3 appears to have reduced the viral genome copies without the need for the continuous administration of drug. Although the treatment with PhenDC3 resulted in some accumulation of cells in late S and G2 phase of the cell cycle, there was minimal cytotoxic effect suggesting that these G-quadruplex stabilizers have possibly exhibited a transient S-phase arrest or cell cycle slow down. This suggests the potential importance of G-quadruplex stabilizing compounds as pharmacological inhibitors of KSHV latent DNA replication and maintenance.