The Contribution of Extracellular Nef to HIV-Induced Pathogenesis

Author(s): Eleonora Olivetta, Claudia Arenaccio, Francesco Manfredi, Simona Anticoli, Maurizio Federico

Journal Name: Current Drug Targets

Volume 17 , Issue 1 , 2016

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Graphical Abstract:


Nef is an accessory protein expressed exclusively in primate lentiviruses. It is devoid of enzymatic activities while interacting with several cell proteins as an adaptor/scaffold protein. Intracellular functions of Nef largely account for many pathogenic effects observed in AIDS disease. Nef, despite lacking known secretory pathways, can be detected in plasma of HIV-1-infected patients at the concentration varing from 5 to 10 ng/ml. Remarkably, the levels of Nef in plasma of HIV patients do not correlate with viral load or number of CD4+ T lymphocytes, and persist during antiretroviral therapy. Here, we review literature data describing how Nef can be transmitted from HIV-1- infected cells to bystander ones, and the effects of extracellular Nef in different cell types. Overall, large part of experimental evidences supports the idea that extracellular Nef plays a relevant role in AIDS pathogenesis. Hence, efforts focused on the identification of Nef-inhibiting drugs would be of relevance to establish new therapeutic approaches supporting current antiretroviral therapies.

Keywords: ADAM17, cell signaling, exosomes, HIV-1 infection, nanotubes, Nef.

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Article Details

Year: 2016
Published on: 17 December, 2015
Page: [46 - 53]
Pages: 8
DOI: 10.2174/1389450116666151001110126

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