Abstract
In R5-tropic clade C simian-human immunodeficiency viruses (SHIV-Cs), we identified a 3-asparagine (3N) deletion mutation in the V2 loop stem of gp120 as the major determinant of neutralization escape of the anti-CD4-binding site (anti-CD4-bs) neutralizing monoclonal antibody (nMAb) b12. However, the more potent anti-CD4-bs nMAbs VRC01 and VRC03 were not sensitive to this mutation. Using isogenic tier 1 or tier 2 proviruses differing only in the 3N mutation, we showed that this mutation might result in selective conformational b12 epitope masking. Therefore, human immunodeficiency virus (HIV) Env immunogens targeting the CD4-bs and designed to neutralize tier 2 viruses should take conformational masking by the V2 loop into account.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Neutralizing / immunology*
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Antibodies, Neutralizing / metabolism
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Binding Sites
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CD4 Antigens / metabolism*
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Epitopes / immunology
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Humans
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Membrane Glycoproteins / chemistry*
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Membrane Glycoproteins / immunology*
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Membrane Glycoproteins / metabolism
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Molecular Sequence Data
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Neutralization Tests
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Protein Conformation
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Sequence Homology, Amino Acid
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Simian Acquired Immunodeficiency Syndrome / immunology
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Simian Acquired Immunodeficiency Syndrome / metabolism
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Simian Acquired Immunodeficiency Syndrome / virology*
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Simian Immunodeficiency Virus / immunology*
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Viral Envelope Proteins / chemistry*
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Viral Envelope Proteins / immunology*
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Viral Envelope Proteins / metabolism
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Virion
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Virus Replication
Substances
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Antibodies, Monoclonal
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Antibodies, Neutralizing
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CD4 Antigens
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Epitopes
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Membrane Glycoproteins
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Viral Envelope Proteins
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gp120 protein, Simian immunodeficiency virus