Ridostin inhibits HIV-1 replication in the T lymphoblastoid cell line C8166. 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 under 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. Ridostin inhibited HIV-1 replication in a concentration range that is 100-fold lower than the toxic concentration for these cells. C8166 cells spontaneously produced interferon (IFN) alpha and gamma, as well as tumor necrosis factor (TNF) alpha. Ridostin activated IFN alpha and suppressed TNF alpha and IFN gamma production by these cells. Monoclonal antibodies (MoAbs) to TNF alpha dose-dependently inhibited HIV-1 replication 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 HIV-1 replication.
Scheglovitova
O
O
Gamaleya Institute for Microbiology and Epidemiology, Moscow, Russia.
Ameglio
F
F
Trento
E
E
Ershov
F
F
D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012331:RNA, Fungal / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D016207:Cytokines; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D012331:RNA, Fungal; D014409:Tumor Necrosis Factor-alpha; C076741:ridostin; D007371:Interferon-gamma