RIDOSTIN INHIBITS HIV-1 REPLICATION IN THE T-LYMPHOBLASTOID CELL-LINEC8166 - POSSIBLE ROLE OF ALTERED CYTOKINE PRODUCTION

Altered cytokine production in human immunodeficiency virus 1 (HIV-1) infection is well documented and cytokine modulators are currently und er investigation as possible therapeutic agents. We tested the ability of Ridostin (dsRNA preparation derived from S. cervisiae) to inhibit HIV-1 replication in acutely infected T lymphoblastoid C8166 cells. Ri dostin inhibited HIV-I replication in a concentration range that is 10 0-fold lower than the toxic concentration for these cells. C8166 cells spontaneously produced interferon (IFN) alpha and gamma, as well as t umor necrosis factor (TNF) alpha. Ridostin activated IFN alpha and sup pressed TNF alpha and IFN gamma production by these cells. Monoclonal antibodies (MoAbs) to TNF alpha dose-dependently inhibited HIV-1 repli cation in these cells. Therefore it is possible that the observed anti -HIV activity of Ridostin in C8166 cells is partly mediated by altered cytokine production. Particularly, suppression of TNF alpha synthesis , that is known to activate HIV-1 replication in several model systems , can play a major role in the observed inhibition of H1V-1 replicatio n.