title: The Contribution of Extracellular Nef to HIV-Induced Pathogenesis.
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.
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. eleonora.olivetta@iss.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Olivetta
authors.forename: Claudia
authors.initials: C
authors.lastname: Arenaccio
authors.forename: Francesco
authors.initials: F
authors.lastname: Manfredi
authors.forename: Simona
authors.initials: S
authors.lastname: Anticoli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Federico
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D024201:Bystander Effect / Q000502:physiology; D055808:Drug Discovery; D055354:Exosomes / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D036341:Intercellular Signaling Peptides and Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1