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B Shan

Publications and source records attributed to B Shan.

38 records · Page 3Linked to original sources
PubMed1989

Interferon-induced expression of different genes is mediated by distinct regulatory pathways.

Interferons (IFNs) regulate the expression of multiple genes and the regulatory sequences associated with several of these genes have been identified. How cell-surface IFN receptors communicate with such regulatory elements is as yet unknown. We have characterized the IFN responses of a mutant murine cell line (Ltk-aprt-) which is unable to mount an antiviral response when treated with IFN-beta. In contrast to its inability to activate antiviral pathways in these cells, IFN-beta inhibits their growth to the same level as observed in their parental L-929 line which is fully responsive to IFN, suggesting that distinct pathways account for antiviral and cytostatic responses. In agreement with this, Northern blot and nuclear run-on analyses show that the induction of transcription of three distinct genes (2,5(A) synthetase, BS-I-150, and BS-II-4) is blocked in Ltk-aprt- cells whereas another gene (I-8) is activated normally. Our results show that the defective responses observed in this cell line are not due to a nonfunctional IFN-beta cell-surface receptor and suggest that multiple pathways exist between the receptor and upstream gene regulatory elements.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Beta and gamma interferons act synergistically to produce an antiviral state in cells resistant to both interferons individually.

We showed previously that the mouse fibroblastoid cell line Ltk-aprt- is resistant to the antiviral effects of beta interferon. This lack of response reflects a partial sensitivity to the interferon that is accompanied by a failure to activate expression of several interferon-regulated genes, although certain other genes respond in a normal manner. We show here that Ltk-aprt- cells were also unable to establish an antiviral state and to activate expression of 2,5-oligo(A) synthetase when treated with gamma interferon. Strikingly, however, treatment with a combination of beta interferon and gamma interferon provided complete protection against viral replication. Although the cells were completely insensitive to up to 250 U of the interferons per ml added singly, essentially complete protection from viral cytopathic effects was achieved when as little as 10 U of each of the interferons per ml were combined. Expression of 2,5-oligo(A) synthetase was also sensitive to this synergistic effect. Activation of an antiviral state could also be achieved by sequential treatment, first with gamma interferon and then with beta interferon. Partial protection against viral replication could be achieved by pretreatment with gamma interferon for as little as 1 h before incubation with beta interferon and could be blocked by the addition of specific antibodies or by cycloheximide, indicating that gamma interferon induces the synthesis of a protein which can act synergistically with a signal produced by the beta-interferon receptor. We suggest that Ltk-aprt- cells suffer from defects in one or more components of the gene activation pathways for both type I and type II interferons. Nonetheless, gamma interferon is able to activate the expression of a gene encoding a protein required for signal transduction. This protein acts synergistically with a transient signal produced in response to beta interferon, thereby activating the expression of a further group of genes.

2',5'-Oligoadenylate Synthetase↗