title: Cell-mediated anti-Gag immunity in pharmacologically induced functional cure of simian AIDS: a 'bottleneck effect'?
abstract: BACKGROUND
  Administration of antiretroviral therapy and two experimental drugs, auranofin and buthionine sulfoximine (BSO), was previously shown to be followed by drug-free control of chronic SIVmac251 infection, decreased immune activation and increased cell-mediated anti-Gag responses.
  
  
  METHODS
  Phylogeny was analysed with Phylogeny.fr. Entropy was calculated with the specific tool of the HIV Sequence Database. The capsid Gag structure was computed using SPDBV. The bottleneck effect was simulated through an appropriate online tool.
  
  
  RESULTS
  The region of Gag predominantly targeted during control of SIVmac251 infection is highly conserved in primate lentiviruses and plays an important role in capsid architecture. Computer-aided simulations support the view that the preferential development of immune responses against this region is derived from a 'bottleneck effect' after restriction, by auranofin and BSO, of the activated lymphocyte pool.
  
  
  CONCLUSIONS
  Restriction of immune activation through auranofin/BSO may result in stochastic selection of cell clones targeting conserved epitopes leading to a functional cure-like condition.
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Iart Luca
authors.initials: IL
authors.lastname: Shytaj
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Savarino
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001310:Auranofin / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D015683:Gene Products, gag / Q000235:genetics* / Q000378:metabolism; D000882:Haplorhini; D007111:Immunity, Cellular / Q000187:drug effects*; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics*
chemical_list: D044966:Anti-Retroviral Agents; D015683:Gene Products, gag; D001310:Auranofin; D019328:Buthionine Sulfoximine
keywords: Gag; auranofin; bottleneck effect; buthionine sulfoximine; conserved sequences; entropy