Methods for modulating expression of an HIV-1 fusion cofactor

Abstract

The invention relates to a method for modulating HIV-1 fusion cofactor expression by manipulating CTLA-4 on the surface of T cells. The invention encompasses methods for modulating HIV-1 fusion cofactor expression by inhibiting one or more intracellular signals resulting from stimulation of CTLA-4. In one embodiment, expression of the HIV-1 fusion cofactor, CCR5, is downregulated by binding of anti-CTLA-4 antibody to CTLA-4.

1 . A method for down-regulating susceptibility to HIV-1 infection comprising the steps of manipulating CTLA4 on the surface of T cells and downregulating the expression of HIV-1 fusion cofactor.  
     
     
         2 . The method of  claim 1 , wherein said HIV-1 fusion cofactor is CCR5.  
     
     
         3 . The method of  claim 1 , wherein said HIV-1 fusion cofactor expression is downregulated.  
     
     
         4 . The method of  claim 1 , wherein said HIV-I fusion cofactor expression is downregulated in vivo.  
     
     
         5 . The method of  claim 1 , wherein said HIV-1 fusion cofactor expression is down-regulated in vitro.  
     
     
         6 . The method of  claim 1 , wherein said CTLA4 on the surface of said T cell is manipulated by the use of an agent that interacts with said CTLA4.  
     
     
         7 . The method of  claim 6 , wherein said agent is an antibody or fragment thereof.  
     
     
         8 . The method of  claim 7 , wherein said anti-CTLA4 antibody binds an epitope on the CTLA-4 molecule comprising the B7-1 or B7-2 binding site.  
     
     
         10 . The method of  claim 7 , wherein said anti-CTLA4 antibody is soluble.  
     
     
         11 . The method of  claim 7 , wherein said anti-CTLA4 antibody is bound to a solid surface.  
     
     
         12 . The method of  claim 11 , wherein said solid surface is a microbead.  
     
     
         13 . A method for treating a subject having an HIV-1 infection, comprising administering to said subject an agent that manipulates a CTLA4-associated signal in the T cells of said subject, thereby treating said subject having an HIV-1 infection.  
     
     
         14 . The method of  claim 13 , wherein said agent is an antibody.  
     
     
         15 . The method of  claim 14 , wherein said antibody is an anti-CTLA4 antibody.  
     
     
         16 . The method of  claim 14 , wherein said anti-CTLA4 antibody binds an epitope on the CTLA4 molecule comprising the B7-1 or B7-2 binding site.  
     
     
         17 . The method of  claim 14 , wherein said anti-CTLA4 antibody is soluble.  
     
     
         18 . The method of  claim 13 , wherein said subject is suffering from chronic HIV-1 infection.  
     
     
         19 . The method of  claim 13 , further comprising determining the levels of CCR5 expression in said subject.  
     
     
         20 . The method of  claim 13 , further comprising determining the level of viral load in said subject.  
     
     
         21 . A method for treating a subject having an HIV-1 infection, comprising obtaining T cells from said subject; and contacting said T cells with an agent that manipulates CTLA4-associated signal in said T cells of said subject, thereby treating said subject having an HIV 1 infection.  
     
     
         22 . The method of  claim 21 , wherein said agent is an anti-CTLA4 antibody or fragment thereof.  
     
     
         23 . The method of  claim 21 , wherein said anti-CTLA4 antibody binds an epitope on the CTLA4 molecule comprising the B7-1 or B7-2 binding site.  
     
     
         24 . The method of  claim 21 , wherein said anti-CTLA4 antibody is soluble.  
     
     
         25 . The method of  claim 21 , further comprising determining the levels of CCR5 expression in said T cells.  
     
     
         26 . The method of  claim 21 , further comprising determining the levels of viral load in said T cells.  
     
     
         27 . A composition for treating HIV comprising an effective amount of agent that manipulates CTLA4 associated signal that downregulates an HIV-1 fusion cofactor expression.  
     
     
         28 . The compound of  claim 27 , wherein said agent is coupled to a solid phase surface.  
     
     
         29 . The compound of  claim 28 , wherein said solid phase surface is a microbead.  
     
     
         30 . The composition of  claim 27 , wherein said agent is an anti-CTLA4 antibody or fragment thereof.  
     
     
         31 . The composition of  claim 27 , wherein said anti-CTLA4 antibody binds an epitope on the CTLA4 molecule comprising the B7-1 or B7-2 binding site.  
     
     
         32 . The method of  claim 29 , wherein said anti-CTLA4 antibody is soluble.