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Title: Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection

HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here in this paper, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of the study period, VRC01-lineage clades showed continuous evolution, with rates of ~2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [4] ;  [4] ;  [3] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] ;  [4] more »;  [5] ;  [6] ;  [4] ;  [4] ;  [7] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] ;  [8] « less
  1. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases, Vaccine Research Center; Rockefeller Univ., New York, NY (United States). Aaron Diamond AIDS Research Center
  2. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases, Vaccine Research Center; Columbia Univ., New York, NY (United States). Dept. of Biochemistry and Molecular Biophysics and Dept. of Systems Biology; Southern Medical Univ., Guangdong (China). Nanfang Hospital, State Key Lab. of Organ Failure Research; Southern Medical Univ., Guangdong (China). Nanfang Hospital, National Clinical Research Center for Kidney Disease
  3. Columbia Univ., New York, NY (United States). Dept. of Biochemistry and Molecular Biophysics and Dept. of Systems Biology
  4. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases, Vaccine Research Center
  5. National Inst. of Health (NIH), Bethesda, MD (United States). National Human Genome Research Inst., NIH Intramural Sequencing Center
  6. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases, Lab. of Immunoregulation
  7. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases, Vaccine Research Center; Columbia Univ., New York, NY (United States). Dept. of Biochemistry and Molecular Biophysics and Dept. of Systems Biology
  8. National Inst. of Health (NIH), Bethesda, MD (United States). National Human Genome Research Inst., NIH Intramural Sequencing Center
Publication Date:
OSTI Identifier:
1221428
Grant/Contract Number:
W-31-109-Eng-38; P01-AI104722
Type:
Accepted Manuscript
Journal Name:
Cell
Additional Journal Information:
Journal Volume: 161; Journal Issue: 3; Journal ID: ISSN 0092-8674
Publisher:
Elsevier
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES