Characterization of CD4-Induced Epitopes on the HIV Type 1 gp120 Envelope Glycoprotein Recognized by Neutralizing Human Monoclonal Antibodies

The entry of human immunodeficiency virus (HIV-1) into target cells typically requires the sequential binding of the viral exterior envelope glycoprotein, gp120, to CD4 and a chemokine receptor. CD4 binding exposes gp120 epitopes recognized by CD4-induced (CD4i) antibodies, which can block virus binding to the chemokine receptor. We identified three new CD4i antibodies from an HIV-1-infected individual and localized their epitopes. These epitopes include a highly conserved gp120 β-strand encompassing residues 419–424, which is also important for binding to the CCR5 chemokine receptor. All of the CD4i antibodies inhibited the binding of gp120–CD4 complexes to CCR5. CD4i antibodies and CD4 reciprocally induced each other’s binding, suggesting that these ligands recognize a similar gp120 conformation. The CD4i antibodies neutralized laboratory-adapted HIV-1 isolates; primary isolates were more resistant to neutralization by these antibodies. Thus, all known CD4i antibodies recognize a common, conserved gp120 element overlapping the binding site for the CCR5 chemokine receptor

Clinical features of HIV-1-infected patients with subtypes A, D, and AD recombinants.

<p>Clinical features of HIV-1-infected patients with subtypes A, D, and AD recombinants.</p

Cox proportional hazards analysis of factors associated with 30-day mortality.

*<p>compared to negative blood cultures.</p

Enrollment procedure.

<p>Enrollment procedure.</p

K-M survival curves comparing mortality between HIV-1 subtypes A vs. D vs. AD recombinants.

<p>K-M survival curves comparing mortality between HIV-1 subtypes A vs. D vs. AD recombinants.</p

Distribution of HIV-1 subtypes among patients with severe sepsis.

<p>Subtype A (n = 81), D (n = 29), AD (n = 53), C (n = 3), AC (n = 2), AB (n = 2), BD (n = 3), CD (n = 2).</p