The Human Immunodeficiency Virus (HIV) invades human T cells via their CD4 receptor. The HIV lipoprotein envelope is composed of glycoproteins gp120 and gp41. The gp120 third variable loop (V3) has been shown to be involved in chemokine receptor finding to CD4 and to other members of the chemokine receptor family, such as CCR5. With the use of gp120 mutants, as well as antibodies against various regions of the viral envelope, Rizzuto et al. have shown that a structure of highly conserved epitopes near the V3 loop is critical to viral biding.
       HIV binds to CCR5 after CD4 binding. Binding to CD4 increases CCR5 binding 100- to 1000-fold. CD4 binding induces neutralization epitopes and causes conformational changes in gp120. These changes make it easier for the virus to bind to CCR5. Using antibodies and amino acid changes, the V3 loop was shown to be needed for CCR5 binding. V1 and V2 are dispensable for CCR5 binding, although CD4 binding has been shown to reposition the V1 and V2 loops to expose epitopes necessary in CCR5 binding. Changes such as an aspartic acid substitution for threonine-123 in the V1/V2 stem slow done viral binding to CCR5.
        Gp120 is composed of an inner and outer domain divided by a bridging sheet, which is a four-stranded, antiparallel beta sheet which included V1 and V2. Rizzuto et al. showed that the CCR5 binding site is composed of conserved amino acids near or within the bridging sheet. Rizzuto et al. concluded that CD4 binding induces conformational changes within the bridging sheet and within the inner and outer domains to form a high-affinity CCR5-bindiing site. Also, interaction of gp120 and g41 is affected by CD4-induced conformational changes, suggesting these changes and gp41 are involved in viral binding.
       The study of the conserved region of gp120 necessary to viral-chemokine binding and of conformational changes induced by CD4 will assist in the development of pharmacological inhibitors of virus-receptor interaction and may prove to be a great step in the fight against HIV infection.

Louiza Patsis, M.S.