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

• Published in: Nature reviews. Microbiology Vol. 7; no. 6; pp. 467 - 476
• Main Author: Kirchhoff, Frank
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.06.2009
• Subjects: Acquired immune deficiency syndrome; AIDS; Animals; Antigens; Apoptosis; Care and treatment; Development and progression; Evolution, Molecular; Gene Products, nef - metabolism; Gene Products, nef - physiology; Genes; Genetic aspects; Genomes; Glycoproteins; Health aspects; HIV; HIV infection; HIV-1 - metabolism; HIV-1 - pathogenicity; Human immunodeficiency virus; Human Immunodeficiency Virus Proteins - metabolism; Human Immunodeficiency Virus Proteins - physiology; Humans; Immunology; Interferon alpha; Lymphocytes; Models, Biological; Pathogens; Proteins; Risk factors; Signal transduction; Simian Immunodeficiency Virus - metabolism; Simian Immunodeficiency Virus - pathogenicity; T cell receptors; T cells; Viral Regulatory and Accessory Proteins - metabolism; Viral Regulatory and Accessory Proteins - physiology; Virulence; Viruses; Germany
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro2111

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-alpha. 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.