Lipopolysaccharide: A Potent Inhibitor of Viral-Mediated Type-I Interferon Induction

Abstract

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.