Differential Regulation of Interferon Synthesis in Lymphoblastoid Cells

Abstract

We have examined the molecular mechanisms involved in the induction and regulation of expression of α and β_l human interferons (HuIFN) in Namalva cells. Cloned IFN-α and -β₁ cDNAs, and antisera to purified IFN-α and -β₁ were used as specific probes to determine the expression of HuIFN genes both on the RNA and protein levels. The rates of gene transcription were correlated with the relative levels of HuIFN mRNA present in induced cells and with the amounts of HuIFN peptides synthesized by these cells. The comparative rate of transcription of HuIFN-α and -β₁ genes was measured in nuclei isolated from Namalva cells before and after induction. No transcription of HuIFN-α and -β₁ genes was detected in nuclei isolated from the uninduced cells. The correspondence in the rate of HuIFN-α and -β₁ genes transcription after virus infection with the relative levels of HuIFN mRNA in the induced cells indicates that the stimulation of HuIFN synthesis by viral infection results from the activation of the transcription of HuIFN genes. The relative levels of α and β₁ induced transcripts were the same in spite of the differences in the number of copies of HuIFN-α and -β₁ genes indicating that the β₁ gene is transcribed more efficiently than the α genes.

The steady-state levels of HuIFN-α and -β₁ mRNAs in induced Namalva cells are comparable, however, the overall amount of HuIFN-β₁ synthesized (as determined by radioimmunoassay and biological activity) is approximately 10-fold lower than that of IFN-α. No evidence has been found that would indicate that HuIFN-β₁ mRNA induced in Namalva cells is different from that induced in human fibroblasts. The data indicate, however, that in Namalva cells, the IFN-β₁ polypeptide has a higher turnover rate and slower rate of release into medium than the HuIFN-α polypeptides, indicating that the observed difference in the overall amounts of these two types of interferons present in the medium is due to regulation on posttranslational level.