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

Jennifer D. Watkins, Juan Diaz-Rodriguez, Siddappa Nagadenahalli Byrareddy, Davide Corti, Ruth M. Ruprecht

Research output: Contribution to journalComment/debate

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)12811-12814
Number of pages4
JournalJournal of virology
Volume85
Issue number23
DOIs
StatePublished - Dec 1 2011

Fingerprint

Simian Immunodeficiency Virus
Human immunodeficiency virus
Neutralizing Antibodies
neutralizing antibodies
binding sites
tropics
Binding Sites
HIV
mutation
Mutation
proviruses
Proviruses
Sequence Deletion
Asparagine
asparagine
neutralization
epitopes
Epitopes
monoclonal antibodies
Monoclonal Antibodies

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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. / Watkins, Jennifer D.; Diaz-Rodriguez, Juan; Byrareddy, Siddappa Nagadenahalli; Corti, Davide; Ruprecht, Ruth M.

In: Journal of virology, Vol. 85, No. 23, 01.12.2011, p. 12811-12814.

Research output: Contribution to journalComment/debate

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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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