We have examined whether the increased activity of the anti-oxidant enzyme SeGPx could influence the course of an acutely spreading HIV infection. Human T cells were genetically engineered to over-express this enzyme by the introduction of a SeGPx expression construct. T cells expressing elevated SeGPx activity displayed an accelerated appearance of HIV-associated cytopathicity as compared to control cells. In addition, SeGPx over-producing cells also exhibited increased kinetics of viral replication. It is hypothesized that these effects are due to the SeGPx-mediated inhibition of the cellular apoptotic response to viral infection as we have obtained similar results with the anti-apoptosis gene bcl-2. In order to evaluate whether the inhibition of SeGPx could retard the progression of an HIV infection, glutathione (the source of reducing equivalents for SeGPx) levels were reduced with BSO. Using non-toxic levels of BSO (20 uM), it was determined that the reduction in glutathione levels could attenuate HIV replication in both immortalized T cells and normal human PBLs. Collectively, these results indicate that alterations in the anti-oxidant defenses of human T cells can influence the progression of an acutely spreading HIV infection and indicate the potential complexity of using selenium or anti-oxidant supplementation as an AIDS therapy.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology