Method for preventing HIV-1 infection of CD4 cells

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. 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 + cells effective to prevent fusion of HIV-1 to CD4 + cells and a pharmaceutically acceptable carrier.

1 - 50 . (canceled) 
     
     
         51 . A monoclonal antibody, or a portion of such antibody, prepared against a human CCR5 chemokine receptor expressed in a mammalian cell line, which receptor binds RANTES, MIP-1α and MIP-1β, and wherein the antibody is capable of inhibiting infection of a human CD4 +  cell by a HIV-1 virus. 
     
     
         52 . The monoclonal antibody, or a portion of such antibody, of claim  1 , which inhibits fusion of the HIV-1 to CD4+ cells, and the HIV-1 is macrophage-tropic. 
     
     
         53 . The monoclonal antibody of claim  1 . 
     
     
         54 . The monoclonal antibody portion of claim  1 . 
     
     
         55 . A composition comprising the monoclonal antibody of  claim 53  and a carrier. 
     
     
         56 . The composition of  claim 55 , wherein the monoclonal antibody is present in an amount effective to inhibit HIV-1 infection. 
     
     
         57 . A composition comprising the monoclonal antibody portion of  claim 54  and a carrier. 
     
     
         58 . The composition of  claim 57 , wherein the monoclonal antibody portion is present in an amount effective to inhibit HIV-1 infection. 
     
     
         59 . An antibody, or a portion of such antibody, which binds to a chemokine receptor which binds RANTES, MIP-1α and MIP-1β, which antibody inhibits infection of a human CD4+ cell by a HIV-1 virus. 
     
     
         60 . The antibody according to  claim 59  which is capable of inhibiting fusion of HIV-1 to CD4+ cells thereby inhibiting HIV-1 infection, and the HIV-1 is macrophage-tropic. 
     
     
         61 . The antibody according to  claim 59 , obtainable by
 i) making a cDNA library in a mammalian expression vector, using mRNA prepared from CD4+ T-lymphocytes or macrophages;   ii) identifying members of the cDNA library encoding members of the chemokine receptor family using appropriate degenerate oligonucleotide probes;   iii) expressing vectors containing chemokine receptor cDNAs in a mammalian cell line which expresses human CD4 but does not fuse with HeLa cells expressing gp120/gp41 from the macrophage-tropic strain HIV JR-FL ;   iv) identifying clones which thereby gain the ability to fuse with HeLa-env JR-FL ;   v) preparing monoclonal or polyclonal antibodies to the thus-expressed receptor;   vi) testing the monoclonal or polyclonal antibodies for ability to inhibit infection by a panel of HIV-1 isolates.   
     
     
         62 . The antibody of  claim 61  which is monoclonal. 
     
     
         63 . A composition comprising the monoclonal antibody of  claim 62  and a carrier.