Opposing regulatory effects of thioredoxin and eosinophil cytotoxicity-enhancing factor on the development of human immunodeficiency virus 1.
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.
Newman
G W
GW
Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Balcewicz-Sablinska
M K
MK
Guarnaccia
J R
JR
Remold
H G
HG
Silberstein
D S
DS
D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D004804:Eosinophils / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013879:Thioredoxins / Q000378:metabolism / Q000494:pharmacology*
D016207:Cytokines; D011994:Recombinant Proteins; D013879:Thioredoxins