OPPOSING REGULATORY EFFECTS OF THIOREDOXIN AND EOSINOPHIL CYTOTOXICITY-ENHANCING FACTOR ON THE DEVELOPMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS-1

Exogenous recombinant human thioredoxin (rTRX, greater than or equal t o 500 nM), a dithiol reductase enzyme, inhibited the expression of hum an immunodeficiency virus (HIV) 1(BaL) in human macrophages (M phi) by 71% (range, 26-100%), as evaluated by p24 antigen production and the integration of provirus at 14 d after infection. The stoichiometric re ducing agent N-acetylcysteine (NAC) also inhibited HIV production, but to a lesser degree, and only at 30,000-fold higher concentrations. Ex ogenous rTRX is cleaved by M phi to generate the inflammatory cytokine , eosinophil cytotoxicity-enhancing factor (ECEF). In contrast to rTRX , rECEF (concentrations from 50 pM to 2 mu M) enhanced the production of HIV by 67% (range, 33-92%). Thus, whereas TRX is a potent inhibitor of the expression of HIV in human M phi, cleavage of TRX to ECEF crea tes a mediator with the opposite effect. TRX also inhibited the expres sion of integrated provirus in the chronically infected OM 10.1 cell l ine, showing that it can act at a step subsequent to viral infection a nd integration.