Identification of drug resistance mutations in HIV from constraints on natural evolution

Thomas C. Butler, John P. Barton, Mehran Kardar, and Arup K. Chakraborty

Phys. Rev. E 93, 022412 – Published 19 February 2016

Abstract

Human immunodeficiency virus (HIV) evolves with extraordinary rapidity. However, its evolution is constrained by interactions between mutations in its fitness landscape. Here we show that an Ising model describing these interactions, inferred from sequence data obtained prior to the use of antiretroviral drugs, can be used to identify clinically significant sites of resistance mutations. Successful predictions of the resistance sites indicate progress in the development of successful models of real viral evolution at the single residue level and suggest that our approach may be applied to help design new therapies that are less prone to failure even where resistance data are not yet available.

3 More

Received 7 August 2015
Revised 4 December 2015

DOI:https://doi.org/10.1103/PhysRevE.93.022412

Physics Subject Headings (PhySH)

Mutation Viral diseases

Viruses

Physics of Living Systems

Authors & Affiliations

Thomas C. Butler^1,2, John P. Barton^1,2,3, Mehran Kardar^1,*, and Arup K. Chakraborty^1,2,3,4,†

¹Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
²Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
³Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02139, USA
⁴Departments of Chemistry and Biological Engineering, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

^*kardar@mit.edu
^†arupc@mit.edu

Article Text (Subscription Required)

Click to Expand

References (Subscription Required)

Click to Expand

Issue

Vol. 93, Iss. 2 — February 2016

Reuse & Permissions

Access Options

Article Available via CHORUS

Download Accepted Manuscript

Author publication services for translation and copyediting assistance advertisement

Physical Review E

covering statistical, nonlinear, biological, and soft matter physics