Innate gastrointestinal immunity: characterization of broadly active viral inhibitors.
Innate viral inhibitors that are broadly active have been characterized in the serum and the nervous system, but incompletely characterized in the gastrointestinal (GI) tract. GI preparations from porcine gastric mucosa, mouse intestine, and in neuramide (a pharmaceutical product), were examined for broad antiviral activity, molecular size and mechanism of action for comparison with the previously characterized, innate inhibitors in the serum and nervous system. The GI inhibitors were found to be active in high titers against RNA and DNA viruses, resistant to proteolysis, glycolysis, lipid extraction and possessed differing mechanisms of action. The mouse intestinal inhibitor prevented virus attachment to cells, and neuramide acted at an early post-attachment stage of virus multiplication. The porcine mucosal inhibitor acted as late as 6 h after initiation of the multiplication cycle. These broadly active GI inhibitors differed from the previously described serum inhibitor (UTI beta) high density lipoproteins (HDL) and the nervous system (NS) inhibitor by being smaller (600 +/- 400 kDa) and resistant to proteinase K, glycosidases and organic solvents. The mouse intestinal inhibitor acts similarly to UTI beta and NS inhibitor by preventing attachment of virus to the cells. In comparison, the neuramide and the porcine mucosal inhibitor, like HDL, acted after attachment to the target cells. The innate nonspecific, broadly-active virus inhibitors, based on high titers and location, are considered important initial immune defense mechanisms against viral infections and thus potentially useful in medical applications.
Singh
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Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019, USA.
Coppenhaver
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Chopra
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Baron
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D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology; D000998:Antiviral Agents / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects; D007113:Immunity, Innate / Q000276:immunology; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D008574:Mengovirus / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D012845:Sindbis Virus / Q000187:drug effects; D013552:Swine; D014616:Vaccinia virus / Q000187:drug effects; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D014775:Virus Activation / Q000187:drug effects / Q000276:immunology
D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D007155:Immunologic Factors; C039202:neuramide