Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design
Name
Chakraborty_Translating HIV.pdf
Size
2.5 MB
Format
Adobe PDF
Checksum (MD5)
7181e45305de1483fa714b5952ab536f
Author(s)
Ferguson, Andrew L.
Mann, Jaclyn K.
Omarjee, Saleha
Ndung'u, Thumbi
Walker, Bruce D.
Chakraborty, Arup K.
Ferguson, Andrew L.
Date Issued
March 2013
Journal
Immunity
Publisher
Elsevier/Cell Press
Citation
Ferguson, Andrew L., Jaclyn K. Mann, Saleha Omarjee, Thumbi Ndung’u, Bruce D. Walker, and Arup K. Chakraborty. “Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design.” Immunity 38, no. 3 (March 2013): 606–617.
Version
Author's final manuscript
Abstract
A prophylactic or therapeutic vaccine offers the best hope to curb the HIV-AIDS epidemic gripping sub-Saharan Africa, but it remains elusive. A major challenge is the extreme viral sequence variability among strains. Systematic means to guide immunogen design for highly variable pathogens like HIV are not available. Using computational models, we have developed an approach to translate available viral sequence data into quantitative landscapes of viral fitness as a function of the amino acid sequences of its constituent proteins. Predictions emerging from our computationally defined landscapes for the proteins of HIV-1 clade B Gag were positively tested against new in vitro fitness measurements and were consistent with previously defined in vitro measurements and clinical observations. These landscapes chart the peaks and valleys of viral fitness as protein sequences change and inform the design of immunogens and therapies that can target regions of the virus most vulnerable to selection pressure.
MIT Department
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.immuni.2012.11.022
