Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants

Naturally occurring human immunodeficiency virus (HIV-1) variants require t he presence of CD4 and specific chemokine receptors to enter a cell. In the laboratory, HIV-1 variants that are capable of bypassing CD4 and utilizing only the CCR5 chemokine receptor for virus entry have been generated. Here we report that these CD4-independent viruses are significantly more sensit ive to neutralization by soluble CD4 and a variety of antibodies. The same amino acid changes in the HIV-1 gp120 envelope glycoprotein determined CD4 independence and neutralization sensitivity. The CD4-independent envelope g lycoproteins exhibited higher affinity for antibodies against CD l-induced gp120 epitopes but not other neutralizing ligands. The CD4-independent enve lope glycoproteins did not exhibit increased lability relative to the wild- type envelope glycoproteins. The utilization of two receptors apparently al lows HIV-1 to maintain a more neutralization-resistant state prior to engag ing CD4 on the target cell, explaining the rarity of CD4 independence in wi ld-type HIV-1.