Enhancement of respiratory syncytial virus-induced cytopathology by trypsin, thrombin, and plasmin.
A series of proteases of diverse substrate specificity were tested for their effect on respiratory syncytial virus-induced cytopathology. Three of the enzymes, thrombin, plasmin, and trypsin, were able to augment significantly the fusion of virus-infected A549 cells. On a concentration basis, thrombin was the most active promoter, followed by plasmin and then trypsin. Hirudin, a specific thrombin inhibitor, blocked the fusion-enhancing property of thrombin, yet had no influence on the basal rate of fusion in the absence of the enzyme. By contrast, the amidine-type inhibitors of trypsin-like proteases, bis(5-amidino-2-benzimidazolyl)-methane (BABIM), blocked not only the thrombin effect, but also the fusion in the thrombin-free controls. The suppressive activity of BABIM was observed at concentrations so low as to exclude any direct inhibitory effect on thrombin itself. These results make it seem very likely that thrombin advances cell fusion by activating a BABIM-sensitive protease. Plasmin and trypsin can be expected to act in a similar manner.
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D005341:Fibrinolysin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D010447:Peptide Hydrolases / Q000494:pharmacology*; D012136:Respiratory Syncytial Viruses; D010253:Respirovirus Infections / Q000209:etiology / Q000473:pathology*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D001562:Benzimidazoles; D006629:Hirudins; C025426:bis(5-amidino-2-benzimidazolyl)methane; D010447:Peptide Hydrolases; D014357:Trypsin; D013917:Thrombin; D005341:Fibrinolysin