[Effect of regulator protein Nef on the viral activity of human immunodeficiency virus]

Despite 25 years of research on human immunodeficiency virus (HIV), the functions of some viral proteins are not fully understood. The role of Nef in the evolution of HIV-1 infection towards immunodeficiency is undeniable; however, the mechanisms involved in this function of Nef remain elusive. The interaction of Nef with a large number of cellular partners disrupts the metabolism of infected cells, including the endocytic pathway, in favor of viral spread. Down-regulation of cell-surface major histocompatibility complex (MHC) molecules by Nef enables infected cells to escape immune surveillance. Nef-induced down-regulation of CD4 increases the infectivity of virions by increasing the incorporation of the envelope glycoproteins into the viral membrane. In addition, Nef increases viral infectivity through a mechanism that is independent of MHC and CD4 down-regulation that nonetheless requires the ability of Nef to interfere with the endocytic process. Overall, these properties promote viral spread in the infected host.