Lipopolysaccharide: a potent inhibitor of viral-mediated type-I interferon induction.
During the course of codifying low pathogenicity avian influenza, viruses were tested for their capacity to induce type-I interferon (IFN) and to measure their content of IFN induction-suppressing particles (ISP). One isolate caused a >10-fold reduction in the yield of IFN from chicken embryonic cells co-infected with a virus that normally induces high yields of IFN. The apparent content of ISP was calculated to be approximately 100-fold higher than the number of physical particles of virus measured as hemagglutinating particles. This unrealistic interpretation prompted us to test for a soluble IFN induction-suppressing activity in the allantoic fluid freed of the virus by centrifugation. Indeed, the IFN induction-suppressing activity remained in the virus-free supernatant. The original virus stock subsequently was found to be contaminated with a Gram-negative bacterium, leading us to test lipopolysaccharide (LPS) as the putative IFN induction suppressor. Pure LPS mimicked in a similar dose-dependent manner the IFN induction-suppressing activity of the original allantoic fluid-derived virus, and the allantoic fluid freed of all virus and bacteria. The inhibition of viral-mediated type-I IFN induction by LPS was observed for viruses from 3 different families. These observations suggest that exposure of a host to endotoxin may compromise the IFN induction response of the innate immune system and thus exacerbate virus infection.
Malinoski
Christopher P
CP
Department of Molecular and Cell Biology, University of Connecticut , Storrs, Connecticut.
Marcus
Philip I
PI
D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D007113:Immunity, Innate / Q000187:drug effects; D005585:Influenza in Birds / Q000276:immunology* / Q000821:virology; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009975:Orthomyxoviridae / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence; D014779:Virus Replication
D007370:Interferon Type I; D008070:Lipopolysaccharides