Is the high virulence of HIV-1 an unfortunate coincidence of primate lentiviral evolution?
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.
Kirchhoff
Frank
F
Institute of Virology, University Clinic of Ulm, Germany. frank.kirchhoff@uniklinik-ulm.de
D000818:Animals; D019143:Evolution, Molecular; D015693:Gene Products, nef / Q000378:metabolism / Q000502:physiology; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D015302:Simian Immunodeficiency Virus / Q000378:metabolism / Q000472:pathogenicity; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism / Q000502:physiology; D000086082:Viroporin Proteins
D015693:Gene Products, nef; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins