Efficiency of neutralizing antibodies targeting the CD4-binding site: influence of conformational masking by the V2 loop in R5-tropic clade C simian-human immunodeficiency virus |
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Authors: | Watkins Jennifer D Diaz-Rodriguez Juan Siddappa Nagadenahalli B Corti Davide Ruprecht Ruth M |
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Institution: | Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. |
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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. |
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