Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth
Copyright policy )Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth
ABSTRACTNeutralizing antibodies elicited by HIV-1 coevolve with viral Envs in distinctive patterns, in some cases acquiring substantial breadth. Here we show that primary HIV-1 Envs, when expressed by simian-human immunodeficiency viruses in rhesus macaques, elicited patterns of Env-antibody coevolution strikingly similar to those in humans. This included conserved immunogenetic, structural and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2-apex mode of recognition like that of human bNAbs PGT145/PCT64-35M. Another rhesus antibody bound the CD4-binding site by CD4 mimicry mirroring human bNAbs 8ANC131/CH235/VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.One sentence summaryVirus-antibody coevolution in rhesus macaques recapitulates developmental features of human antibodies.
- National Institutes of Health United States
- Boston University United States
- National Institute of Health Pakistan
- University of Pennsylvania United States
- Boston College United States
570, Binding Sites, Cryoelectron Microscopy, Molecular Mimicry, HIV Infections, HIV Antibodies, HIV Envelope Protein gp120, Virus Replication, Macaca mulatta, Biological Coevolution, Epitopes, CD4 Antigens, HIV-1, Animals, Humans, Simian Immunodeficiency Virus, Broadly Neutralizing Antibodies
570, Binding Sites, Cryoelectron Microscopy, Molecular Mimicry, HIV Infections, HIV Antibodies, HIV Envelope Protein gp120, Virus Replication, Macaca mulatta, Biological Coevolution, Epitopes, CD4 Antigens, HIV-1, Animals, Humans, Simian Immunodeficiency Virus, Broadly Neutralizing Antibodies
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