Orchestrated efforts on host network hijacking: Processes governing virus replication

Dai, Xiaofeng; Hakizimana, Olivier; Zhang, Xuanhao; Kaushik, Aman Chandra; Zhang, Jianying

The S phase of cell cycle provides optimal conditions required for virus replication as DNA synthesis takes place in the S phase and virus DNA replication depends on the host DNA replication machinery. Promoting host cell cycle from the G0/G1 phase into the S phase is indispensable for some viruses such as polyomavirus which do not encode replication proteins. The pRb and TP53 pathways are critical in the control of transiting cells from one phase to another. Some viruses produce viral proteins to suppress these signalings to promote cell cycle transition from the G0/G1 phase into the S phase. For example, the E1A proteins of AAV inactivate the pRb checkpoint to allow E2F activating genes involved in nucleotide metabolism and DNA replication to prepare materials needed for DNA synthesis in the S phase, and interact with transcriptional modulators of cell cycle to prevent cell cycle arrest and apoptosis by stabilizing TP53 [112] . Similarly, HPVs employ E6, E7 and E5 [113] and polyomavirus takes advantage of large T-Ag and small t-Ag [114] in promoting cells transit toward the S phase.