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Is the high virulence of HIV-1 an unfortunate coincidence of primate lentiviral evolution?

Nature Reviews Microbiology volume 7, pages 467–476 (2009)Cite this article

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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Figure 1: Schematic of the functions of Nef and Vpu.
Figure 2: Evolutionary link between the presence of a vpu gene and the lack of Nef-mediated down-modulation of CD3.
Figure 3: Acquisition of vpu and loss of Nef-mediated CD3 down-modulation in the lentiviral lineage that gave rise to HIV-1.
Figure 4: Possible link between Nef and Vpu function in T cell 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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  1. Frank Kirchhoff is at the Institute of Virology, University Clinic of Ulm, 89081 Ulm, Germany. frank.kirchhoff@uniklinik-ulm.de,

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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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