title: Positive in vivo selection of the HIV-1 envelope protein gp120 occurs at surface-exposed regions.
abstract: 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 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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, Zürich, CH-8091, Switzerland. huldrych.guenthard@usz.ch
authors.forename: Beda
authors.initials: B
authors.lastname: Joos
authors.forename: Marek
authors.initials: M
authors.lastname: Fischer
authors.forename: Andreas
authors.initials: A
authors.lastname: Schweizer
authors.forename: Herbert
authors.initials: H
authors.lastname: Kuster
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Alexandra
authors.initials: A
authors.lastname: Trkola
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D019143:Evolution, Molecular; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics*; D015658:HIV Infections; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary / Q000187:drug effects; D020539:Sequence Analysis, Protein
chemical_list: D044966:Anti-Retroviral Agents; D015699:HIV Envelope Protein gp120