HHV-6B protein DR6 identified as inducer of cell cycle arrest in G2/M
While it is known that HHV-6B infection inhibits cellular proliferation at the G2/M phase, no protein had previously been identified as a causative agent to enact this inhibition. In a new article published in Virology this month, Dr. Hollsberg’s team at Aarhus University in Denmark has identified the protein responsible for this crucial mechanism of cell-cycle specific interruption. Through a series of findings, the group has identified the protein product of direct repeat 6, DR6, as an inhibitor of G2/M cell-cycle progression.
The group initially determined that transfection of DR6 reduced the total number of cells compared with mock-transfected cells. Lentiviral transduction of DR6 inhibited host cell DNA synthesis in a p53-independent manner, and this inhibition was DR6 dose-dependent. A deletion of 66 amino acids from the N-terminal part of DR6 prevented efficient nuclear translocation and the ability to inhibit DNA synthesis. DR6-induced accumulation of cells in G2/M was accompanied by an enhanced expression of cyclin B1 that accumulated predominantly in the cytoplasm. Pull-down of cyclin B1 brought down pCdk1 with the inactivating phosphorylation at Tyr15. Together, it is evident that DR6 delays the cell cycle, resulting in an accumulation of cells in G2/M and thus is likely involved in HHV-6B-induced cell-cycle arrest.
For more information, read the full paper.