AZT inhibits the transmission of human T cell leukaemia/lymphoma virus type I to adult peripheral blood mononuclear cells in vitro

The effect of 3'-azido-3'-deoxythymidine (AZT) on in vitro infection of peripheral blood mononuclear cells (PBMCs) isolated from normal adult individuals with human T cell leukaemia/lymphoma virus type I (HTLV-I) was evaluated. Different PBMC samples were exposed to HTLV-I by cocultivation with MT-2 (a chronically infected cell line) in the presence of 20 U/ml of human recombinant interleukin 2 (IL-2) and graded concentrations of AZT. Control and drug-treated cultures, of both infected and uninfected PBMCs, were then grown for several weeks and monitored for virological and immunological parameters. The results showed a concentration-dependent anti-proliferative effect of AZT in both infected and non-infected cultures. Production of both proviral DNA and viral RNA was inhibited not only at the higher concentrations of AZT (8 mu M and 32 mu M) but also at concentrations as low as 0.1-2 mu M. These results were confirmed by PCR and by Row cytometry analysis for the viral core protein pig. Moreover, treatment with AZT resulted in a decreased expression of CD25 in cultures exposed to HTLV-I as well as in non-infected PBMCs. On the other hand, HLA-DR was down-regulated to a greater extent in drug-treated, virus-exposed cultures in comparison with those not infected. No evidence of the antiviral activity of AZT was observed in PBMC cultures already infected by HTLV-I or in MT-2 cells. These findings demonstrate that treatment with AZT, when given at the time of infection with HTLV-I, has a marked protective effect on PBMCs.