Abstract: This invention provides an expression vector encoding a CD4-gamma2 chimeric heavy chain homodimer. This invention also provides an expression vector encoding the heavy chains of a CD4-IgG2 chimeric heterotetramer. Finally, this invention provides an expression vector encoding the light chains of a CD4-IgG2 chimeric heterotetramer.

Abstract: This invention provides agents determined to be capable of inhibiting the fusion of a macrophage-tropic primary isolate of HIV-1 to a CD4+cell and agents determined to be capable of inhibiting the fusion of a T cell-tropic isolate of HIV-1 to a CD4+cell. This invention also provides methods to identify such agents. This invention further provides methods of inhibiting fusion of a macrophage-tropic primary isolate of HIV-1 with a CD+ cell and methods of inhibiting fusion of a T cell-tropic isolate of HIV-1 with a CD4+cell susceptible to infection by a T cell-tropic isolate of HIV-1.

Abstract: This invention provides methods for inhibiting fusion of HIV-1 to CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited. This invention also provides methods for inhibiting HIV-1 infection of CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited, thereby inhibiting the HIV-1 infection. This invention provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells.

Abstract: This invention provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention also provides an immunoconjugate which comprises 1) a gamma radiation-emitting radionuclide of low to moderate cytotoxicity and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention further provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a heterotetramer comprising two heavy chains and two light chains, both heavy chains being either 1) IgG2 heavy chains or b) chimeric CD4-IgG2 heavy chains, and both light chains being either a) kappa light chains or b) chimeric CD4-kappa light chains.

Abstract: This invention provides an antibody capable of specifically inhibiting the fusion of an HIV-1 envelope glycoprotein cell with an appropriate CD4+ cell without cross reacting with the HIV-1 envelope glycoprotein or CD4 and capable of inhibiting infection by one or more strains so HIV-1. This antibody is then used to identify a molecule which is important for HIV infection. Different uses of the antibody and the molecule are described.

Abstract: Previous studies of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein-mediated membrane fusion have focused on laboratory-adapted T-lymphotropic strains of the virus. The goal of this application was to develop a novel screening assay to characterize membrane fusion mediated by a primary HIV-1 isolate in comparison with a laboratory-adapted strain. To this end, a novel fusion assay was developed on the basis of the principle of resonance energy transfer, using HeLa cells stably transfected with gp120/gp41 from the T-lymphotropic isolate HIV-1LA1 or the macrophage-tropic primary isolate HIV-1JR-FL. These cells fused with CD4+ target cell lines with a tropism mirroring that of infection by the two viruses. Of particular note, HeLa cells expressing HIV-1JR-FL gp120/gp41 fused only with PM1 cells, a clonal derivative of HUT 78, and not with other T-cell or macrophage cell lines.

Abstract: This invention provides the CD4-IgG2 chimeric heterotetramer, wherein the heavy chains of the chimeric heterotetramer is encoded by the expression vector designated CD4-IgG2HC-pRcCMV (ATCC No. 75193). This invention also provides the CD4-IgG2 chimeric heterotetramer, wherein the light chains of the chimeric heterotetramer is encoded by the expression vector designated CD4-kLC-pRcCMV (ATCC No. 75194). This invention also provides the CD4-IgG2 chimeric heterotetramer, wherein the heavy chains of the chimeric heterotetramer is encoded by the expression vector designated CD4-IgG2HC-pRcCMV (ATCC No. 75193) and the light chains of the chimeric heterotetramer is encoded by the expression vector designated CD4-kLC-pRcCMV (ATCC No. 75194).

Abstract: This invention provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention also provides an immunoconjugate which comprises 1) a gamma radiation-emitting radionuclide of low to moderate cytotoxicity and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention further provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a heterotetramer comprising two heavy chains and two light chains, both heavy chains being either a) IgG2 heavy chains or b) chimeric CD4-IgG2 heavy chains, and both light chains being either a) kappa light chains or b) chimeric CD4-kappa light chains.

Abstract: This invention provides methods for inhibiting fusion of HIV-1 to CD4.sup.+ cells which comprise contacting CD4.sup.+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4.sup.+ cells is inhibited. This invention also provides methods for inhibiting HIV-1 infection of CD4.sup.+ cells which comprise contacting CD4.sup.+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4.sup.+ cells is inhibited, thereby inhibiting the HIV-1 infection. This invention provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4.sup.+ cells. This invention also provides pharmaceutical compositions comprising an amount of the non-chemokine agent capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4.sup.+ cells effective to prevent fusion of HIV-1 to CD4.sup.

Abstract: An immunoconjugate which consists of a cytotoxic radionuclide and a homodimer comprising two heavy chains, the cytotoxic radionuclide being linked to the heavy chains dirctly or using a bifunctional chelator and a composition which comprises the immunoconjugate and an acceptable carrier.

Abstract: This invention provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention also provides an immunoconjugate which comprises 1) a gamma radiation-emitting radionuclide of low to moderate cytotoxicity and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention further provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a heterotetramer comprising two heavy chains and two light chains, both heavy chains being either a) IgG2 heavy chains or b) chimeric CD4-IgG2 heavy chains, and both light chains being either a) kappa light chains or b) chimeric CD4-kappa light chains.

Abstract: The subject invention provides a recombinant nucleic acid molecule which encodes a mutant HIV-1 gp120 envelope glycoprotein comprising a V3 loop deletion and a C4 domain.sub.(W.fwdarw.X) point mutation wherein X is an amino acid residue other than tryptophan, and the HIV-1 gp120 envelope glycoprotein encoded thereby.The subject invention further provides a method of obtaining partially purified antibodies which specifically bind to the CD4-binding domain of HIV-1 gp120 envelope glycoprotein, the partially purified antibodies produced thereby, and pharmaceutical compositions comprising same. Finally, the subject invention provides methods of treating HIV-1-infected subjects, and of reducing the likelihood of HIV-1-exposed and non-HIV-1-exposed subjects' becoming infected with HIV-1 using the pharmaceutical compositions of the subject invention.

Abstract: The subject invention provides a recombinant nucleic acid molecule which encodes a mutant HIV-1 gp120 envelope glycoprotein comprising a V3 loop deletion and a C4 domain.sub.(W.fwdarw.X) point mutation wherein X is an amino acid residue other than tryptophan, and the HIV-1 gp120 envelope glycoprotein encoded thereby.The subject invention further provides a method of obtaining partially purified antibodies which specifically bind to the CD4-binding domain of HIV-1 gp120 envelope glycoprotein, the partially purified antibodies produced thereby, and pharmaceutical compositions comprising same. Finally, the subject invention provides methods of treating HIV-1-infected subjects, and of reducing the likelihood of HIV-1-exposed and non-HIV-1-exposed subjects' becoming infected with HIV-1 using the pharmaceutical compositions of the subject invention.

Abstract: The invention is directed to compositions containing CD4-based immunoconjugates and antibodies specific for the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). The CD4-based immunoconjugates comprise a portion obtained from CD4 conjugated to a heavy or light chain region obtained from IgG2. The CD4-immunoconjugates can be CD4-IgG2 chimeric heavy chain homodimers whose chains are encoded by the expression vector designated CD4-IgG2-pcDNA1 having ATCC Accession No. 40952, or heterotetramers having chimeric heavy chains encoded by the expression vector designated CD4-IgG2HC-pRcCMV having ATCC Accession No. 75193 and chimeric light chains encoded by the expression vector designated CD4-kLC-pRcCMV having ATCC Accession No. 75194. The compositions of the invention act synergistically to neutralize HIV-1.