G0/G1 host cell cycle checkpoint dysregulation by virus (kw:KW-1077)

Host cell cycle is a highly regulated process during which chromosomes duplicated and cell division occurs. Resting cells that are not dividing are in a phase called G0. During division, the cell undergoes 4 distinct stages termed G1, S, G2, and M (mitosis). These periods of activity are separated by regulatory checkpoints at major transition phases. These checkpoints include G0/G1 which regulates the entry of a quiescent cell back into the cycle, G1/S, and G2/M.

Some viruses have evolved strategies to induce cell cycle entry in resting cells by promoting the G0/G1 checkpoint transition. For example, myxomavirus M-T5 mediates cell cycle progression beyond the G0/G1 checkpoint, with increased phosphorylation, ubiquitination and degradation of the cyclin-dependent kinase inhibitor p27/KIP1. HTLV-1 Tax induces also a cell cycle progression from G0/G1 phase.

Other viruses benefit from stopping host cells in G0/G1 checkpoint. For example SARS protein 3a inhibits Rb phosphorylation and blocks cell cycle progression at the G0/G1 phase. Epstein-Barr virus BZLF1 (Zta) mediates a G0/G1 growth arrest correlated with a p21 induction. Murine coronavirus p28 expression results in an accumulation of hypophosphorylated Rb and cyclin-dependent kinase (Cdk) inhibitor p21.