Interferon- and sarcolectin-dependent cellular regulatory interactions.
Interferons, via specific membrane-bound receptors, induce various cellular functions of which antiviral protection is the most extensively studied. We have previously reported the existence of interferon antagonists (referred to as sarcolectins) in various tissue extracts from placental blood, cartilage, brain, muscle, or from sarcomas. These sarcolectins have been fully characterized and purified to homogeneity. In interferon-treated cells, they restore virus sensitivity 4-6 h after the establishment of antiviral protection. In the present study we investigate the effect of sarcolectins on the steady state levels of two double-stranded RNA dependent enzymes, 2-5A (p chi (A2'p)nA) synthetase and protein kinase. Several authors have previously emphasized the role of these enzymes in the mechanism of interferon's antiviral action. Interferon promotes a 4-8 fold increase in protein kinase and 2-5A synthetase in cells. Addition of sarcolectin 5 h after interferon results in a dramatic reduction in the steady state levels of both these enzymes, as shown by their decreased activity and yield observed in Western blot assays. The degradation of the antiviral response in sarcolectin-treated cells might therefore be at least partially attributed to a reduced synthesis of protein kinase and 2-5A synthetase. Since there are no direct interactions between sarcolectins and interferon or its receptors, it can be postulated that sarcolectins exert their effect through these interferon-dependent proteins. We postulate that the opposing biological effects of interferon and sarcolectins strike a balance which may, however, be modified in one direction or the other, depending on their respective concentrations.
Jiang
P H
PH
Institut National de la Santé de la Recherche Médicale, Unité 43, Hôpital Saint Vincent de Paul.
Chany-Fournier
F
F
Galabru
J
J
Robert
N
N
Hovanessian
A G
AG
Chany
C
C
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D007372:Interferons / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008970:Molecular Weight; D011494:Protein Kinases / Q000378:metabolism
D000998:Antiviral Agents; D037102:Lectins; C039495:sarcolectin; D007372:Interferons; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase