CC chemokine receptor 5 DNA, new animal models and therapeutic agents for HIV infection

Abstract

The susceptibility of human macrophages to human immunodeficiency virus (HIV) infection depends on cell surface expression of the human CD4 molecule and CC cytokine receptor 5. CCR5 is a member of the 7-transmembrane segment superfamily of G-protein-coupled cell surface molecules. CCR5 plays an essential role in the membrane fusion step of infection by some HIV isolates. The establishment of stable, nonhuman cell lines and transgenic mammals having cells that coexpress human CD4 and CCR5 provides valuable tools for the continuing research of HIV infection. In addition, antibodies which bind to CCR5, CCR5 variants, and CCR5-binding agents, capable of blocking membrane fusion between HIV and target cells represent potential anti-HIV therapeutics for macrophage-tropic strains of HIV.

What is claimed is:  
     
         1 . An isolated polynucleotide which encodes an amino acid sequence as set forth in SEQ ID NO:2 or SEQ ID NO:4.  
     
     
         2 . An isolated polynucleotide selected from the group consisting of: 
 a) SEQ ID NO:1;    b) SEQ ID NO:3;    c) SEQ ID NO:1, wherein T can also be U;    d) SEQ ID NO:3, wherein T can also be U;    e) nucleic sequences complementary to SEQ ID NO:1;    f) nucleic sequences complementary to SEQ ID NO:3;    g) fragments of a), c), or e) that are at least 15 bases in length and that will selectively hybridize to genomic DNA which encodes the CCR5 protein of SEQ ID NO:2; and    h) fragments of b), d), or f) that are at least 15 bases in length and that will selectively hybridize to genomic DNA which encodes the CCR5 protein of SEQ ID NO:4.    
     
     
         3 . The polynucleotide of  claim 2 , wherein the polynucleotide fragments encode a peptide selected from the group consisting of AAQWDFGNTMC (SEQ ID NO:4), RSQKEGLHYTCSSHFPYSQYQFWK (SEQ ID NO:5), and QEFFGLNNCSSSNRLD (SEQ ID NO:6).  
     
     
         4 . An expression vector containing in operable linkage the polynucleotide as in  claim 1 .  
     
     
         5 . A host cell containing the vector of  claim 4.