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Identification of CCR5 ECL2 residues critical to HIV-1 entry

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center




  • C Dogo-Isonagie
  • S Lam
  • C Bewley


HIV infection requires the initial interactions of viral envelope glycoprotein gp120 with both CD4 and CCR5. The amino terminus of CCR5 binds HIV-1 gp120 at the base of the V3 loop while CCR5 extracellular loop 2 (ECL2) has been implicated to interact with the tip of V3 loop and/or the bridging sheet. Through screening CCR5 ECL2168-191 derived peptides in pseudo-typed virus entry assays, we show that peptides bearing sequences C-terminal from CCR5 Cys178 suppress viral entry. Furthermore, these C-terminal peptides exhibited low M neutralizing activity toward R5, R5X4, and X4 strains. Meanwhile, residues N-terminal from CCR5 Cys178 did not alter viral fusion. Complementary to these cell-based results, we have also identified the CCR5 ECL2 residues directly involved in binding to HIV-1 gp120 through application of Saturation Transfer Difference NMR. Our results indicate that there are common structural elements that mediate viral infectivity of R5, R5X4, and X4 strains.

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