Nef, the shuttling molecular adaptor of HIV, influences the cytokine network

•Effects of extracellular recombinant Nef in cell culture systems.•Nef cell to cell transfer.•Nef influence on the cytokine network and TNFα production.•Nef and type I IFN production in HIV infection.

Several viruses manipulate host innate immune responses to avoid immune recognition and improve viral replication and spreading. The viral protein Nef of Human Immunodeficiency Virus is mainly involved in this “hijacking” activity and is a well established virulence factor. In the last few years there have been remarkable advances in outlining a defined framework of its functions. In particular Nef appears to be a shuttling molecular adaptor able to exert its effects both on infected and non infected bystander cell. In addition it is emerging fact that it has an important impact on the chemo-cytokine network. Nef protein represents an interesting new target to develop therapeutic drugs for treatment of seropositive patients. In this review we have tried to provide a unifying view of the multiple functions of this viral protein on the basis of recently available experimental data.