Human immunodeficiency virus type 1 (HIV 1) has evolved to encode multifunctional accessory proteins to promote the viral life cycle. Nef, a HIV 1 encoded accessory protein that originally thought to be a negative factor that inhibited viral replications, has been reported increasing HIV1 viral particle infectivity through a still unknown mechanism. Recently, lots of experimental evidences showed that Nef could extensively interact with multiple key factors of protein intracellular trafficking pathways, such as adaptor protein families (APs), to promote the HIV pathogenesis through down-regulation of the membrane localization of MHC1 and CD4 molecules. Taking together with the current progresses of the biological nature of Nef in recent years, here, we proposed that the Nef also could increase the infectivity of viral particle possibly through affecting the protein transport pathways of HIV1 factors or other host cellular factors that promote viral assembly or budding. If true, this will let us better understand how Nef manipulate the host cell environment to promote the HIV pathogenicity and will also provide more choices for developing novel therapeutic strategies. © 2009 Elsevier Ltd. All rights reserved.
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