Cells resistant to interferon are defective in activation of a promoter-binding factor.
Human cultured cell lines deficient in their ability to respond to type I interferon (IFN) fail to interrupt cellular proliferation or to induce an antiviral state following exposure to IFN alpha. Comparison of non-responsive Daudi and HeLa cell lines with IFN-responsive partner cell lines and examination of non-responsive Raji cells showed that the defective cell lines expressed type I IFN receptors of typical number and affinity and bound IFN equivalently compared to the normal cells. However, transcriptional induction of interferon-stimulated genes (ISGs) was greatly reduced and delayed in these cell lines, leading to reduced accumulation of ISG mRNA. Furthermore, the rapid activation of IFN-stimulated promoter binding factors whose appearance correlates with ISG transcriptional induction, did not occur in non-responsive cells. Thus, the primary defect of these cells leading to an impaired physiological response to IFN appears to be an inability to activate promoter-binding factors necessary to trigger ISG transcription, an obligate early step in antiviral and antiproliferative physiology.
Kessler
D S
DS
Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021.
Pine
R
R
Pfeffer
L M
LM
Levy
D E
DE
Darnell
J E
JE
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D004351:Drug Resistance; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology; D017471:Receptors, Interferon; D014158:Transcription, Genetic / Q000187:drug effects*
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017471:Receptors, Interferon