Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes.
Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses.
Department of Chemical Engineering, MIT, Cambridge, Massachusetts 02139, USA and Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02129, USA.
Karthik
K
Shekhar
Department of Mathematics, Pomona College, Claremont, California 91711, USA.
Claire F
CF
Ruberman
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Andrew L
AL
Ferguson
Department of Chemical Engineering, MIT, Cambridge, Massachusetts 02139, USA and Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02129, USA.
John P
JP
Barton
Department of Physics, MIT, Cambridge, Massachusetts 02139, USA.
Mehran
M
Kardar
Department of Chemical Engineering, MIT, Cambridge, Massachusetts 02139, USA and Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02129, USA and Department of Physics, MIT, Cambridge, Massachusetts 02139, USA and Department of Chemistry, MIT, Cambridge, Massachusetts 02139, USA and Department of Biological Engineering, MIT, Cambridge, Massachusetts 02139, USA and Institute for Medical Engineering and Science, MIT, Cambridge, Massachusetts 02139, USA.
Arup K
AK
Chakraborty
D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D040901:Proteomics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014765:Viral Vaccines / Q000276:immunology
D014764:Viral Proteins; D014765:Viral Vaccines