Exogenous recombinant human thioredoxin (rTRX, > or = 500 nM), a dithiol reductase enzyme, inhibited the expression of human immunodeficiency virus (HIV) 1BaL 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 reducing agent N-acetylcysteine (NAC) also inhibited HIV production, but to a lesser degree, and only at 30,000-fold higher concentrations. Exogenous 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 microM) 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 creates a mediator with the opposite effect. TRX also inhibited the expression of integrated provirus in the chronically infected OM 10.1 cell line, showing that it can act at a step subsequent to viral infection and integration.
Opposing regulatory effects of thioredoxin and eosinophil cytotoxicity-enhancing factor on the development of human immunodeficiency virus 1.
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G W Newman, M K Balcewicz-Sablinska, J R Guarnaccia, H G Remold, D S Silberstein; Opposing regulatory effects of thioredoxin and eosinophil cytotoxicity-enhancing factor on the development of human immunodeficiency virus 1.. J Exp Med 1 July 1994; 180 (1): 359–363. doi: https://doi.org/10.1084/jem.180.1.359
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