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Positive In Vivo Selection of the HIV-1 Envelope Protein gp120 Occurs at Surface-Exposed Regions

Joos, Beda ; Fischer, Marek ; Schweizer, Andreas ; Kuster, Herbert ; Böni, Jürg ; Wong, Joseph K. ; Weber, Rainer ; Trkola, Alexandra ; Günthard, Huldrych F.

In: The Journal of Infectious Diseases, 2007, vol. 196, no. 2, p. 313-320

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    Titre
    • Positive In Vivo Selection of the HIV-1 Envelope Protein gp120 Occurs at Surface-Exposed Regions
    Auteur
    • Joos, Beda. Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital ZürichZürich, Switzerland
    • Fischer, Marek. Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital ZürichZürich, Switzerland
    • Schweizer, Andreas. Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital ZürichZürich, Switzerland
    • Kuster, Herbert. Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital ZürichZürich, Switzerland
    • Böni, Jürg. Swiss National Center for RetrovirusesZürich, Switzerland
    • Wong, Joseph K.. San Francisco Veterans Affairs Medical Center, University of CaliforniaSan Francisco
    • Weber, Rainer. Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital ZürichZürich, Switzerland
    • Trkola, Alexandra. Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital ZürichZürich, Switzerland
    • Günthard, Huldrych F.. Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital ZürichZürich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • The Journal of Infectious Diseases, 2007, vol. 196, no. 2, p. 313-320. The University of Chicago Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:295696
    Summary
    The rapid evolution of human immunodeficiency virus (HIV) envelope represents a major challenge to vaccine and drug development, particularly because the underlying mechanisms are not completely understood. To explore whether distinct patterns of positive selection within the envelope protein glycoprotein (gp) 120 exist and are associated with functionally relevant domains, we conducted a long-term survey of sequence evolution in 20 HIV-1-infected persons who interrupted antiretroviral therapy. In total, 1753 clonal sequences encompassing the C2-V3-C3 region of gp120 were derived. Strikingly, positively selected amino acids mapped almost exclusively (P=.0003) to externally accessible residues on the gp120 crystal structure. The current understanding of envelope structure and function associates the main determinants of viral entry and the targets for neutralizing antibodies with these exterior regions of gp120, strongly suggesting that the observed adaptive evolution of these sites occurs in response to respective selective forces