Manipulation of the cell cycle by HIV-1

Many viruses manipulate the host cell cycle to enhance viral replication and promote their evasion of host immune defenses. Human immunodeficiency virus type 1 (HIV-1) is no exception and triggers cell cycle arrest during its infection of replicating CD4+ T cells, acting predominantly through the activities of the viral proteins Vpr and Vif. Here, we summarize HIV-1's effects on cell cycle regulation, focusing on the distinct mechanisms that underpin Vpr and Vif's modulation of cell cycle checkpoints. We also discuss how these activities, when combined, may help the virus to enhance replication and promote reactivation from long-term latency-the major barrier to a cure for HIV/AIDS. A deeper understanding of how HIV-1 remodels the host cell cycle should reveal important new cell biology and may inform the development of therapeutic strategies relevant to curative interventions.