Rational design of a CD4 mimic that inhibits HIV-1 entry and exposes cryptic neutralization epitopes

Loïc Martin, François Stricher, Dorothée Missé, Francesca Sironi, Martine Pugnière, Philippe Barthe, Rafael Prado-Gotor, Isabelle Freulon, Xavier Magne, Christian Roumestand, André Ménez, Paolo Lusso, Francisco Veas, Claudio Vita

Research output: Contribution to journalArticlepeer-review

Abstract

The conserved surfaces of the human immunodeficiency virus (HIV)-1 envelope involved in receptor binding represent potential targets for the development of entry inhibitors and neutralizing antibodies. Using structural information on a CD4-gp120-17b antibody complex, we have designed a 27-amino acid CD4 mimic, CD4M33, that presents optimal interactions with gp120 and binds to viral particles and diverse HIV-1 envelopes with CD4-like affinity. This mini-CD4 inhibits infection of both immortalized and primary cells by HIV-1, including primary patient isolates that are generally resistant to inhibition by soluble CD4. Furthermore, CD4M33 possesses functional properties of CD4, including the ability to unmask conserved neutralization epitopes of gp120 that are cryptic on the unbound glycoprotein. CD4M33 is a prototype of inhibitors of HIV-1 entry and, in complex with envelope proteins, a potential component of vaccine formulations, or a molecular target in phage display technology to develop broad-spectrum nuetralizing antibodies.

Original languageEnglish
Pages (from-to)71-76
Number of pages6
JournalNature Biotechnology
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2003

ASJC Scopus subject areas

  • Microbiology

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