Molecular determinants of nef function

The human immunodeficiency virus (HIV), the causative agent of the acquired immune deficiency syndrome (AIDS), in addition to encoding for thegag, pol andenv structural genes common to all retroviruses also encodes six accessory genes:tat, rev, nef, vpr, vpu andvif. These accessory genes are responsible for the regulation of HIV replication. Recent advances in our understanding of the function(s) of these genes have illustrated the complex interplay between HIV, the infected cell and the host. In addition, identification of cellular proteins interacting with accessory gene products have provided new tools to study cellular processes. The topic of this review,nef, has been shown in vitro to induce the cell surface downregulation of CD4, the receptor for HIV, to enhance the infectivity of HIV particles and to associate with at least one cellular serine/threonine kinase. In vivo, Nef is essential for the efficient virus replication responsible for disease progression. In this review, several prominent aspects of Nef function are discussed including its effect on CD4 trafficking, on signaling pathways and on virus infectivity enhancement.