Understanding the nature of the Nef requirement for HIV-1 infectivity

Background Nef is an HIV-1 accessory protein with a fundamental role for virus replication in vivo and for the development of AIDS. Among its several activities, Nef is essential for maintaining HIV-1 maximal infectivity. In cell culture, such activity can account for as much as 98% of the HIV-1 virion infectivity and requires Nef to be expressed in virus producing cells rather than in target cells. However, the cause of the defective infectivity of Nef-negative HIV-1 and the mechanism by which Nef is able to restore such a defect remain elusive. The purpose of this research is to establish whether Nef contributes to HIV-1 infectivity by counteracting a cellular inhibitor or by promoting a cellular activity required for optimal infectivity.