Innate gastrointestinal immunity: characterization of broadly active viralinhibitors

Innate viral inhibitors that are broadly active have been characterized in the serum and the nervous system, but incompletely characterized in the gas trointestinal (GI) tract. GI preparations from porcine gastric mucosa, mous e intestine, and in neuramide (a pharmaceutical product), were examined for broad antiviral activity, molecular size and mechanism of action for compa rison with the previously characterized, innate inhibitors in the serum and nervous system. The GI inhibitors were found to be active in high titers a gainst RNA and DNA viruses, resistant to proteolysis, glycolysis, lipid ext raction and possessed differing mechanisms of action. The mouse intestinal inhibitor prevented virus attachment to cells, and neuramide acted at an ea rly post-attachment stage of virus multiplication. The porcine mucosal inhi bitor acted as late as 6 h after initiation of the multiplication cycle. Th ese broadly active GI inhibitors differed from the previously described ser um inhibitor (UTI beta) high density lipoproteins (HDL) and the nervous sys tem (NS) inhibitor by being smaller (600 +/- 400 kDa) and resistant to prot einase K, glycosidases and organic solvents. The mouse intestinal inhibitor acts similarly to UTI beta and NS inhibitor by preventing attachment of vi rus to the cells. In comparison, the neuramide and the porcine mucosal inhi bitor, like HDL, acted after attachment to the target cells. The innate non specific, broadly-active virus inhibitors, based on high titers and locatio n, are considered important initial immune defense mechanisms against viral infections and thus potentially useful in medical applications. (C) 2001 E lsevier Science B.V. All rights reserved.