Abstract
In the subset of primate lentiviruses that contain a vpu gene — HIV-1 and its simian precursors — the Nef protein has lost the ability to down-modulate CD3, block T cell activation and suppress programmed death. Vpu counteracts a host restriction factor induced by the inflammatory cytokine interferon-α. I propose that the acquisition of vpu may have allowed the viral lineage that gave rise to HIV-1 to evolve towards greater pathogenicity by removing the selective pressure for a protective Nef function that prevents damagingly high levels of immune activation.
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Acknowledgements
I thank B. H. Hahn and G. Silvestri for helpful comments, E. Bailes for providing phylogenetic trees, and M.L. Wilson, C. Neel and M. Peeters for providing photographs of non-human primates. I also thank all present and past members of my laboratory, as well as all my collaborators, for their contributions to the work discussed in this article. I apologize to the authors of the many interesting studies that could not be cited owing to space limitations. I am supported by grants from the Deutsche Forschungsgemeinschaft, the Wilhelm Sander Foundation, the European Community and the National Institutes of Health.
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Kirchhoff, F. Is the high virulence of HIV-1 an unfortunate coincidence of primate lentiviral evolution?. Nat Rev Microbiol 7, 467–476 (2009). https://doi.org/10.1038/nrmicro2111
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