Abstract
The effects of sera from 20 patients with acquired immunodeficiency syndrome (AIDS) and 33 patients with AIDS-related complex (ARC) on human immunodeficiency virus (HIV-1) reverse transcriptase (RT) were studied. The results of RT assays showed strong inhibiting and enhancing effects of some of these sera on HIV-1 RT activity in vitro. The modulating effects were not observed in assays containing sera taken from HIV-1 uninfected homosexuals, suggesting that the inhibitory and enhancing phenomena are associated with HIV-1 infection. The present study has focused on the inhibitory function of the sera. Kinetic enzymatic study showed that the inhibitory sera contained one or more heat-resistent (56°C, 30min) inhibitors, which display a high affinity for protein A. These results suggest that the inhibitor (s) is probably an anti-HIV-1 RT antibody that inhibit RT activity. Further, sera were tested for the presence of neutralizing activity against HIV-1 infection. For the neutralizing activity assay, HIV-1 infection of human T cell line (H 9) was assessed by monitoring DNA synthesis of H 9 cells, viable cell counts, HIV-1 gag protein expression, and RT activity in the supenatant. The RT inhibitory antibody seems to contribute partially to the sera's neutralizing activity against HIV-1. Sera from AIDS subjects that displayed RT inhibiting effects showed significantly greater neutralizing activity that sera displaying RT enhancing effects or no effects. The existence of an antibody that inhibits RT activity suggests a novel approach to the development of antiviral agents, and its apparent correlation with neutralizing capacity may present new possibilities for anti-HIV-1 vaccines. In addition, the recognition of this inhibitory phenomenon brings to light potential methodological problems involving both clinical and experimental uses of RT assays.
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