title: Scaling laws describe memories of host-pathogen riposte in the HIV population.
abstract: The enormous genetic diversity and mutability of HIV has prevented effective control of this virus by natural immune responses or vaccination. Evolution of the circulating HIV population has thus occurred in response to diverse, ultimately ineffective, immune selection pressures that randomly change from host to host. We show that the interplay between the diversity of human immune responses and the ways that HIV mutates to evade them results in distinct sets of sequences defined by similar collectively coupled mutations. Scaling laws that relate these sets of sequences resemble those observed in linguistics and other branches of inquiry, and dynamics reminiscent of neural networks are observed. Like neural networks that store memories of past stimulation, the circulating HIV population stores memories of host-pathogen combat won by the virus. We describe an exactly solvable model that captures the main qualitative features of the sets of sequences and a simple mechanistic model for the origin of the observed scaling laws. Our results define collective mutational pathways used by HIV to evade human immune responses, which could guide vaccine design.
authors: Departments of Chemical Engineering, Physics, Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139.
authors: John P
authors: JP
authors: Barton
authors: Physics, arupc@mit.edu kardar@mit.edu.
authors: Mehran
authors: M
authors: Kardar
authors: Departments of Chemical Engineering, Physics, Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139 Chemistry, and Biological Engineering, and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139; and arupc@mit.edu kardar@mit.edu.
authors: Arup K
authors: AK
authors: Chakraborty
mesh_terms: D006678:HIV / Q000302:isolation & purification / Q000502:physiology*; D015658:HIV Infections / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans
keywords: HIV; evolution; fitness landscape; host–pathogen interaction; neural networks
references: Nature. 2006 Apr 20;440(7087):1007-12
references: 16625187
references: J Virol. 2009 Aug;83(15):7641-8
references: 19458000
references: Immunity. 2013 Mar 21;38(3):606-17
references: 23521886
references: Nature. 1991 Dec 12;354(6353):453-9
references: 1721107
references: Lancet Infect Dis. 2012 Jan;12(1):36-44
references: 22032844
references: Cold Spring Harb Perspect Med. 2012 Nov;2(11). pii: a007054. doi: 10.1101/cshperspect.a007054
references: 23002014
references: Proc Natl Acad Sci U S A. 1982 Apr;79(8):2554-8
references: 6953413
references: Science. 2008 May 9;320(5877):760-4
references: 18467582
references: Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17441-6
references: 17954909
references: Nature. 2014 Mar 6;507(7490):57-61
references: 24572367
references: Phys Rev E Stat Nonlin Soft Matter Phys. 2013 Dec;88(6):062705
references: 24483484
references: Nat Med. 2004 Mar;10(3):275-81
references: 14966520
references: Hum Immunol. 2007 Sep;68(9):779-88
references: 17869653
references: Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5405-10
references: 20212159
references: Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11530-5
references: 21690407
references: Phys Rev A Gen Phys. 1989 Aug 15;40(4):2082-2087
references: 9902366
references: Br Med Bull. 2001;58:19-42
references: 11714622
references: PLoS One. 2009;4(8):e6687
references: 19690614
references: Phys Rev Lett. 2011 Mar 4;106(9):090601
references: 21405611
references: J Virol. 2003 Feb;77(3):2081-92
references: 12525643
references: Immunity. 2012 Sep 21;37(3):426-40
references: 22999948
references: J Theor Biol. 1988 Dec 7;135(3):265-81
references: 3256719
references: Nature. 1999 Nov 18;402(6759):255-62
references: 10580495
references: PLoS Comput Biol. 2014 Aug;10(8):e1003776
references: 25102049