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Research Article

Genetic Signatures in the Envelope Glycoproteins of HIV-1 that Associate with Broadly Neutralizing Antibodies

  • S. Gnanakaran,

    Affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America

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  • Marcus G. Daniels,

    Affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America

    X
  • Tanmoy Bhattacharya,

    Affiliations: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America, Santa Fe Institute, Santa Fe, New Mexico, United States of America

    X
  • Alan S. Lapedes,

    Affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America

    X
  • Anurag Sethi,

    Affiliations: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America, Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America

    X
  • Ming Li,

    Affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America

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  • Haili Tang,

    Affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America

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  • Kelli Greene,

    Affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • Hongmei Gao,

    Affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • Barton F. Haynes,

    Affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • Myron S. Cohen,

    Affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

    X
  • George M. Shaw,

    Affiliations: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America

    X
  • Michael S. Seaman,

    Affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America

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  • Amit Kumar,

    Affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America

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  • Feng Gao,

    Affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • David C. Montefiori,

    Affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • Bette Korber mail

    btk@lanl.gov

    Affiliations: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America, Santa Fe Institute, Santa Fe, New Mexico, United States of America

    X
  • Published: October 07, 2010
  • DOI: 10.1371/journal.pcbi.1000955

About the Authors

S. Gnanakaran, Marcus G. Daniels, Tanmoy Bhattacharya, Alan S. Lapedes, Anurag Sethi, Bette Korber
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America
Tanmoy Bhattacharya, Bette Korber
Santa Fe Institute, Santa Fe, New Mexico, United States of America
Anurag Sethi
Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America
Ming Li, Haili Tang, Kelli Greene, Hongmei Gao, David C. Montefiori
Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America
Barton F. Haynes, Amit Kumar, Feng Gao
Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America
Myron S. Cohen
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
George M. Shaw
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
George M. Shaw
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Michael S. Seaman
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America

Corresponding Author

Email: btk@lanl.gov

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: DCM BK. Performed the experiments: DCM BK. Analyzed the data: SG MGD TB ASL BK. Contributed reagents/materials/analysis tools: BFH MSC GMS MSS AK FG DCM BK. Wrote the paper: DCM BK. Protein modeling and interpretation of signatures: SG. Signature analysis, programming, modified decision forest strategy: MGD. Theory, analysis, and statistical strategies: TB. Theory and statistical strategies, conditional mutual information: ASL. Protein modeling related to electrostatic potential: AS. Cloning and sequencing of Envs in pseudoviruses: ML HT. Provided technical support: HT. Provided project coordination, collected and maintained a database for virus and associated information: KG HG. Design and oversight of clinical studies that were a source of serum samples from HIV-1-infected subjects: BFH MSC GMS. Oversaw neutralization assays with b12: MSS. Single genome amplification and sequencing of gp160 genes in plasma samples; subtyping analysis of the sequences: AK FG. Initial concept, study design, oversaw neutralization assays with HIV-1-positive serum samples, interpretation of signatures: DCM. Initial concept, study design, theory, analysis and interpretation: BK. Co-wrote the original draft of the paper: BK DCM.