Relief of cytotoxicity and enhancement of interferon inducer activity of double-stranded RNA by eukaryotic initiation factor 2.
Double-stranded RNA (dsRNA) is a powerful interferon inducer but also possesses toxic properties. dsRNA was shown previously to inhibit translation by causing the inactivation of eukaryotic initiation factor 2 (eIF-2) and to bind tightly to this protein. The cytotoxicity of dsRNA was analyzed simultaneously with the induction of interferon in murine fibroblast cultures. Incubation of dsRNA with eIF-2 leads to a significant reduction in toxicity, concomitant with a marked stimulation of interferon induction. The enhancement of dsRNA-dependent interferon induction by eIF-2 is sensitive to a monoclonal antibody directed against the beta-subunit of eIF-2. When injected in combination with dsRNA, eIF-2 potentiates the dsRNA-dependent survival of mice infected with a lethal dose of Mengo virus.
Harary
R
R
Department of Molecular Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Gonsky
R
R
Itamar
D
D
Kaempfer
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D004769:Enterovirus Infections / Q000401:mortality; D015852:Eukaryotic Initiation Factor-2 / Q000494:pharmacology*; D007369:Interferon Inducers / Q000494:pharmacology*; D008574:Mengovirus; D051379:Mice; D012330:RNA, Double-Stranded / Q000494:pharmacology / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D015852:Eukaryotic Initiation Factor-2; D007369:Interferon Inducers; D012330:RNA, Double-Stranded