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The molecular determinants of HIV envelope protein gp120 binding Integrin-α4β7

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center




  • F Nawaz
  • C Cicala
  • M Pasuccio
  • D Wei
  • D Van Ryk
  • S Shrestha
  • J Knox
  • K Jelicic
  • A Fauci
  • J Arthos


More than two decades after the isolation of HIV, an estimated 30-million people remain infected worldwide. Thus there exists an urgent need for a vaccine. Our laboratory previously reported that HIV binds to Integrin-α4β7, the gut homing receptor, on the surface of CD4+ T-cells. Subsequently, we showed that α4β7high/CD4+ T-cells are Ki67+, and propagate viral infection more readily than α4β7low/CD4+ T-cells. Understanding the precise manner by which the virus binds α4β7 may therefore provide insights for novel therapeutics. The natural ligands for Integrin-α4β7 bind via a tripeptide, aspartic acid-containing epitope (LDV, VLD, or IDS). To study HIV-gp120 binding to α4β7, we made site-directed aspartic acid mutants in recombinant subtype A, B and C HIV-gp120s, and measured the binding of each mutant to α4β7 on the lymphocyte surface. By this approach, we identified two epitopes that mediate gp120-α4β7 interaction. A single aspartic acid mutant at either position reduced reactivity with α4β7 by ~2-fold relative to the wildtype, while the double aspartic acid mutant diminished α4β7 binding to near-undetectable levels. This observation was consistent in gp120s from all three subtypes, revealing the conservation and complexity in the gp120-α4β7 epitope, advancing upon our previous understanding, and laying the groundwork for further study.

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