title: Error catastrophe and phase transition in the empirical fitness landscape of HIV.
abstract: We have translated clinical sequence databases of the p6 HIV protein into an empirical fitness landscape quantifying viral replicative capacity as a function of the amino acid sequence. We show that the viral population resides close to a phase transition in sequence space corresponding to an "error catastrophe" beyond which there is lethal accumulation of mutations. Our model predicts that the phase transition may be induced by drug therapies that elevate the mutation rate, or by forcing mutations at particular amino acids. Applying immune pressure to any combination of killer T-cell targets cannot induce the transition, providing a rationale for why the viral protein can exist close to the error catastrophe without sustaining fatal fitness penalties due to adaptive immunity.
authors: Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors: Gregory R
authors: GR
authors: Hart
authors: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors: Andrew L
authors: AL
authors: Ferguson
mesh_terms: D019277:Entropy; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D044367:Phase Transition; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1