Mapping genetic determinants for human immunodeficiency virus type 1 resistance to soluble CD4

Neutralization of human immunodeficiency virus type 1 (HIV-1) infection with soluble CD4 (sCD4) can be achieved over a broad range of concentrations for different virus strains. Laboratory virus strains passaged in transformed T-cell lines are typically sensitive to sCD4 neutralization, whereas primary virus isolates require over 100-fold-higher sCD4 concentrations. Using recombinant viruses generated from a laboratory strain, HIV-lNLA,3, and a primary macrophagetropic strain, HIV-1JRFL5, we mapped a region of gpl20 important for determining sensitivity to sCD4 neutralization. This same region has previously been defined as important for macrophage and transformed T-cell line tropism and includes the V3 neutralization domain but does not include regions of gpl20 that have been shown to be most important for CD4 binding. The CD4 molecule is the principal receptor for human immunodeficiency virus type 1 (HIV-1) on peripheral blood lymphocytes (PBL), mononuclear phagocytes, and trans-formed T-cell lines (12, 22, 26). Interaction of the extracel-lular HIV-1 envelope (Env) glycoprotein gpl20 with CD4 is necessary for infection of these cells (7, 8, 25, 35). A truncated, recombinant soluble CD4 (sCD4) was shown t