Compositions and methods for detecting and treating hiv infections

Abstract

HIV infection can be detected by measuring phosphorylation levels of the actin-depolymerizing factor (AFD)/cofilin family, and infection can be treated and/or prevented by modulating the HIV co-receptor signaling pathway.

1 . A method for treating and/or preventing HIV infection in a patient, comprising: administering to said patient an agent that inhibits HIV trigger receptor signaling, inhibits actin depolymerization; enhances the assembly of actin; stabilizes actin filaments; induces polymerization of monomeric actin; binds to F-actin or cofilin; or inhibits actin and cofilin activity. 
     
     
         2 . The method of  claim 1 , wherein said agent is selected from the group consisting of jasplakinolide, PD59, FK506; wortmannin, LY294002, PP2, PP2A, PP1, AG1478, AG1296; slingshot phosphatases, FR225659, fostriecin, calyculin A, cantharidin, jasplakinolide; phaloidin; chondramides, chondramide A, B, C, and D; (−)-doliculide; dolastatin-11; dolastatin 3-Nor; majusculamide; dolastatin Hmp; alpha-cyano-3,4-dihydroxy-N-benzylcinnamide (AG490); 1,2,3,4,5,6-; JSI-124; benzylidenemalonitriles (“tyrphostins”); WHI-P154; WHI-P151; pyrrolo[2,3-d]-pyrimidines; benzimisazo[4,5-f]isoquinolinone derivatives; AG1801; WP1034; WP1050; WP1015; WP1-1066; WP1129; WP1130; WP1119; WP1026; WP1127; JSI-124; cucurbitacin I; cucurbitacin A; cucurbitacin B; cucurbitacin D; cucurbitacin E; tetrahydro-cucurbitacin I; PD98059 (2′-amino-3′-methoxyflavone); UO126; SL327; olomoucine; 5-iodotubercidin; arctigenin; 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives; N3 alkylated benzimidazole derivatives; FR225659; fostriecin; Calyculin A; okadaic acid; cantharidin; TCM-platinum agents containing demethylcantharidin; genistein; MEK inhibitor, and derivatives thereof. 
     
     
         3 . The method of  claim 1 , wherein said agent inhibits the JAC2 signaling pathway. 
     
     
         4 . The method of  claim 1 , wherein said agent inhibits the tyrosine kinase signaling pathway. 
     
     
         5 . The method of  claim 1 , wherein said agent is a phosphatase inhibitor. 
     
     
         6 . The method of  claim 1 , wherein said agent inhibits the Rac/Pac1/Lmk signaling pathway. 
     
     
         7 . The method of  claim 1 , wherein said agent inhibits the signal transduction activity of CXCR4. 
     
     
         8 . A method for identifying compounds that inhibit HIV infection, comprising evaluating a compound's ability to alter the phosphorylation state of a protein of the ADF/cofilin family. 
     
     
         9 . The method of  claim 8 , wherein the evaluation comprises determining whether the compound can inhibit the dephosphorylation of serine-3 residue of cofilin. 
     
     
         10 . A composition comprising:
 a) an effective amount of a compound selected from the group consisting of: jasplakinolide, PD59, FK506; wortmannin, LY294002, PP2, PP2A, PP1, AG1478, AG1296; slingshot phosphatases, FR225659, fostriecin, calyculin A, cantharidin, jasplakinolide; phaloidin; chondramides, chondramide A, B, C, and D; (−)-doliculide; dolastatin-11; dolastatin 3-Nor; majusculamide; dolastatin Hmp; alpha-cyano-3,4-dihydroxy-N-benzylcinnamide (AG490); 1,2,3,4,5,6-; JSI-124; benzylidenemalonitriles (“tyrphostins”); WHI-P154; WHI-P151; pyrrolo[2,3-d]-pyrimidines; benzimisazo[4,5-f]isoquinolinone derivatives; AG1801; WP1034; WP1050; WP1015; WP1-1066; WP1129; WP1130; WP1119; WP1026; WP1127; JSI-124; cucurbitacin I; cucurbitacin A; cucurbitacin B; cucurbitacin D; cucurbitacin E; tetrahydro-cucurbitacin I; PD98059 (2′-amino-3′-methoxyflavone); UO126; SL327; olomoucine; 5-iodotubercidin; arctigenin; 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives; N3 alkylated benzimidazole derivatives; FR225659; fostriecin; Calyculin A; okadaic acid; cantharidin; TCM-platinum agents containing demethylcantharidin; genistein; MEK inhibitor, and derivatives thereof;   b) an effective amount of an anti-retroviral agent; and   c) a pharmaceutically acceptable excipient.