Journal article
Modeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus (HIV-1) Neutralization Efficiency
Cell host & microbe, Vol.14(5), pp.547-558
11/13/2013
DOI: 10.1016/j.chom.2013.10.006
PMCID: PMC3875163
PMID: 24237700
Abstract
Efforts to prevent human immunodeficiency virus (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral envelope glycoprotein (Env) trimer and Env reactivity to bound antibody influence neutralization susceptibility. In addition, we define an antibody-specific parameter, the perturbation factor (PF), that describes the degree of conformational change in the Env trimer required for a given antibody to bind. Minimally perturbing (low-PF) antibodies can efficiently neutralize viruses with a broad range of Env reactivities due to fast on-rates and high affinity for Env. Highly perturbing (high-PF) antibodies inhibit only viruses with reactive (perturbation-sensitive) Envs, often through irreversible mechanisms. Accounting for these quantifiable viral and antibody-associated parameters helps to predict the observed profiles of HIV-1 neutralization by antibodies with a wide range of potencies.
Details
- Title: Subtitle
- Modeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus (HIV-1) Neutralization Efficiency
- Creators
- Hillel Haim - University of Iowa, Microbiology and ImmunologyIgnacio Salas - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215, USAKathleen McGee - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215, USANoah Eichelberger - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAElizabeth Winter - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USABeatriz Pacheco - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215, USAJoseph Sodroski - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215, USA
- Resource Type
- Journal article
- Publication Details
- Cell host & microbe, Vol.14(5), pp.547-558
- DOI
- 10.1016/j.chom.2013.10.006
- PMID
- 24237700
- PMCID
- PMC3875163
- ISSN
- 1931-3128
- eISSN
- 1934-6069
- Grant note
- U19 AI067854 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID T32 AI007386 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID P30 AI060354 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R37 AI024755 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 11/13/2013
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984208550902771
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