Functional roles of Nef beyond HIV

February 10, 2012
2:30 p.m.

Nef is a multifunctional regulatory protein exclusively encoded by primate lentiviruses and critical for AIDS progression. In addition to the ability to promote the downregulation of cell surface receptors and to alter the activation state of the cell, Nef modulates the infectivity of virus particles with a mechanism which remains unknown and which has been the main subject of our research.
In this seminar I will describe how we recently discovered that other proteins, encoded by divergent retroviruses, have a Nef-like activity on virion infectivity, providing a compelling example of convergent evolution.
In an effort to unveil the molecular mechanism triggered by these viral proteins, we then identified a host factor, crucial for intracellular vesicle biogenesis, recruited by Nef and instrumental for its activity on infectivity. Furthermore, while searching for modifications of the viral particle triggered by Nef, we discovered a novel function, shared by such Nef-like proteins, which lead to an increased resistance of retroviruses to powerful neutralizing antibodies targeting a sensitive region of the envelope glycoprotein.