Binding of HTLV-III/LAV to T4 ⁺ T Cells by a Complex of the 110K Viral Protein and the T4 Molecule

Abstract

Human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV) is tropic for human T cells with the helper-inducer phenotype, as defined by reactivity with monoclonal antibodies specific for the T4 molecule. Treatment of T4+ T cells with monoclonal antibodies to T4 antigen blocks HTLV-III/LAV binding, syncytia formation, and infectivity. Thus, it has been inferred that the T4 molecule itself is a virus receptor. In the present studies, the surfaces of T4+ T cells were labeled radioactively, and then the cells were exposed to virus. After the cells were lysed, HTLV-III/LAV antibodies were found to precipitate a surface protein with a molecular weight of 58,000 (58K). By blocking and absorption experiments, this 58K protein was identified as the T4 molecule. No cell-surface structures other than the T4 molecule were involved in the antibody-antigen complex formation. Two monoclonal antibodies, each reactive with a separate epitope of the T4 molecule, were tested for their binding capacities in the presence of HTLV-III/LAV. When HTLV-III/LAV was bound to T4+ T cells, the virus blocked the binding of one of the monoclonal antibodies, T4A (OKT4A), but not of the other, T4 (OKT4). When HTLV-III/LAV was internally radiolabeled and bound to T4+ T cells which were then lysed, a viral glycoprotein of 110K (gp110) coprecipitated with the T4 molecule. The binding of gp110 to the T4 molecule may thus be a major factor in HTLV-III/LAV tropism and may prove useful in developing therapeutic or preventive measures for the acquired immune deficiency syndrome.

HIV-1 Entry and Macrophage Inflammatory Protein-1β-mediated Signaling Are Independent Functions of the Chemokine Receptor CCR5

“…The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (4,5). The HIV-1 exterior glycoprotein, gp120, binds the cellular receptor CD4 (6).…”

Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines.

“…How does this complexity relate to current understanding of the role of CD4 expression as a determinant of HIV sensitivity? The CD4 antigen, through interaction with the glycosylated (13, 32) gp120 envelope protein of HIV, acts as a receptor for free HIV on a subset of T cells, and on cells induced to express CD4 by transfer ofthe CD4 cDNA (1,2,4,(24)(25)(26)(27)(28) . CD4 expression is also necessary for HIV-induced cell fusion (29)(30)(31)(32)(33).…”

“…The CD4 protein acts as a receptor for HIV by virtue of the specific interaction between the OKT4A epitope of CD4 and the HIV envelope protein gp120 (1,2,4,(24)(25)(26)(27)(28) . The low frequency of CD4 expression by HIV-susceptible WIL-2-derived cell lines, and conversely, the HIV insensitivity of some CEM derivatives that ex- pressed CD4 abundantly, prompted us to examine the OKT4A-inhibitable binding of purified, 1251-labeled gp120 by these cell lines (Fig.…”

Mass Spectrometric Characterization of a Discontinuous Epitope of the HIV Envelope Protein HIV-gp120 Recognized by the Human Monoclonal Antibody 1331A

“…A critical step of HIV infection involves the binding of the envelope protein HIV-gp120 to receptors on its target cells (1,2). The glycoprotein HIV-gp120 contains ϳ500 amino acids with varying numbers of attached high mannose and complex-type oligosaccharides (3).…”