Nitric oxide enhances HIV-1 replication in peripheral blood mononuclear cells

Addition of nitric oxide generators (SNP or SNAP) to HIV-1 infected PBMC cu lture produced a significant increase in viral replication and this effect was not associated to a change in PBMC proliferation. Moreover, HIV-1 repli cation was partially prevented by the specific NOS inhibitor L-NMMA or L-NI L. We also have observed that NO leads to HIV-1 replication in transfected T cells with pNL strain and activated; with phorbol ester+ionomycin or TNF. Thus, SNP and SNAP strongly potentiated HIV-1 replication in a dose-depend ent manner to levels comparable to TNF-alpha stimulation. Furthermore, iNOS inhibitors prevented HIV-I replication in HIV-1 transfected cells. Moreove r, HIV-1 induced iNOS in PBMC and MT-2 cells and NO increased LTR-driven tr anscription. Interestingly, L-NIL and L-NMMA inhibited TNF-alpha. So, our r esults suggest that NO is involved in TNF-induced activation of HIV-1 repli cation.