Envelope proteins from clinical isolates of human immunodeficiency virus type 1 that are refractory to neutralization by soluble CD4 possess high affinity for the CD4 receptor.

Abstract

Recent evidence indicates that primary clinical isolates of human immunodeficiency virus type 1 (HIV-1) require significantly more soluble CD4 (sCD4) to block infection than the prototypic laboratory strain HTLV-IIIB. The currently accepted explanation for these observations is that the envelope glycoproteins from primary clinical isolates possess lower affinities for CD4 than laboratory strains. This observation has far reaching implications for the clinical effectiveness of sCD4. To test whether the resistance of clinical isolates to sCD4 neutralization correlates with low-affinity binding to gpl20, we have compared gpl20 glycoproteins derived from the clinical isolates HIV-1 JR-CSF and JR-FL with those derived from the prototypic strain HIV-1 BH10 in quantitative sCD4 binding studies. Surprisingly, our results demonstrate that gpl20 derived from HIV-1 JR-CSF and JR-FL possess sCD4 binding affinities of equal or greater magnitude than gpl20 derived from HIV-i BH10. Thus primary clinical HIV-1 isolates can and do possess gpl20 with high affinity for CD4, and sensitivity to neutralization by sCD4 is dependent upon factors other than the intrinsic affinity of gpl20 for CD4.

Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements

“…The role of entry is favoured by genetic studies in which the determinants of tropism map to the env region Liu et al, 1990;O'Brien et al, 1990;Chesebro et al, 1991;Hwang et al, 1991 ;Shioda et al, 1991 ;Westervelt et al, 1991), although alterations in the structure of the envelope glycoproteins might conceivably influence the assembly of virions at late stages of replication. The precise stage at which tropism is determined is undefined but generally perceived to be a post-binding event, given that all isolates have in common a high affinity for CD4 (Brighty et al, 1991;Ivey-Hoyle et al, 1991;Moore et al, 1992). Fusion of the viral and cellular membranes is a candidate step, although a recent study using fluorescence dequenching suggests that tropism is determined by a post-fusion event (Potash et al, 1992).…”

Human T-Cell Leukemia Virus Type 1 Receptor Expression among Syncytium-Resistant Cell Lines Revealed by a Novel Surface Glycoprotein-Immunoadhesin

“…Previously, Drosophila melanogaster cells have been used to express a variety of lentiviral surface glycoproteins (2,3,23), and it was found that in each case the recombinant envelope protein retained receptor-binding activity and that the affinity of these receptor-ligand interactions correlate with the biological properties of the viral isolates from which they were derived (2,23). Moreover, the recombinant envelope proteins produced in this insect system faithfully recapitulate the immunological, biochemical, and receptor-binding properties of the native virally expressed envelope glycoprotein or envelope glycoproteins expressed in heterologous mammalian expression systems (2,23).…”

“…Moreover, the recombinant envelope proteins produced in this insect system faithfully recapitulate the immunological, biochemical, and receptor-binding properties of the native virally expressed envelope glycoprotein or envelope glycoproteins expressed in heterologous mammalian expression systems (2,23). We have now used this system to express a recombinant epitope-tagged form of the HTLV-1 SU that retains the receptor binding properties of the native viral protein while providing a well-defined antigenic epitope for which immunological reagents are widely available.…”

Molecular determinants of human immunodeficiency virus type I phenotype variability

“…Gp120 from macrophage-tropic HIV-1 isolates binds to CD4 with similar affinity as gp120 from T-cell line-tropic HIV-1 isolates [115,116]. This implicates that replication of T-cell-tropic isolates in macrophages and macrophage-tropic isolates in T-cell lines is restricted at some level after CD4 binding.…”