: The introduction of combination antiretroviral therapy has been largely responsible for the decline of AIDS defining diagnosis in recent years. However, it is clear that while current combination retroviral therapy suppresses HIV replication, viral reservoirs persist in the infected host and virus resurgence will occur when treatment is interrupted. Prolonged treatment with current drugs against HIV reverse transcriptase and protease has unfortunately been associated with complication from adverse side effects and morbidity and the use of these medications has been limited by the development of resistance. As the face of HIV therapeutics is changing, we will need new targets besides reverse transcriptase and protease against HIV. It is increasingly being recognized that the accessory genes of HIV (vif, vpr, vpu and nef) play important roles in modulating viral pathogenesis in vivo. Because they interact with host cellular pathways to maximize viral replication and/or evade the host immune response, unraveling their mechanism may suggest novel ways of interfering with the replication cycles of HIV within the host. Vpr has been shown to delay cells in the G2 phase of the cell cycle. Manipulation of the host's cell cycle is a highly conserved property of Vpr alleles from all primate lentiviruses studied to date, suggesting that this must confer an advantage to the viral replication cycle within the host. This proposal aims at further understanding the mechanism of how Vpr interacts with host cellular factors that normally control progression of the host's cell cycle and explores if drugs that target the function of these cellular factors similarly modify Vpr functions.
| Goh, Wei Chun; Manel, Nicolas; Emerman, Michael (2004) The human immunodeficiency virus Vpr protein binds Cdc25C: implications for G2 arrest. Virology 318:337-49 |
